On December 10, 2021 iTeos Therapeutics, Inc. (Nasdaq: ITOS), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of highly differentiated immuno-oncology therapeutics for patients, reported the presentation of new preclinical data for its anti-TIGIT monoclonal antibody, EOS-448, at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition and the TIGIT Therapies Digital Summit 2021 (Press release, iTeos Therapeutics, DEC 10, 2021, View Source [SID1234596766]).

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"The data we presented this week at the TIGIT Therapies Digital Summit provide further evidence of the multifaceted mechanism of our high affinity, potent anti-TIGIT monoclonal antibody, EOS-448. We presented preclinical data showing activation of immune stimulatory cells is dependent on activating via FcγR, and also show clinically that this activation is translating to depletion of immunosuppressive cells. Furthermore, the upcoming data presentations at ASH (Free ASH Whitepaper) demonstrate the synergistic effect of combining an FcγR active anti-TIGIT antibody with an IMiD in a preclinical model of multiple myeloma and provide strong rationale for our ongoing Phase 1/2 trial in this difficult to treat cancer," said Michel Detheux, Ph.D., president and chief executive officer of iTeos. "These results underscore our enthusiasm for EOS-448 as a potential therapy capable of harnessing the immune system to help improve outcomes for patients with advanced, aggressive cancers. We look forward to progressing our clinical development plan in 2022 in both multiple myeloma and solid tumors with several combinations."

ASH 2021:

The Combination of Anti-Tigit and Lenalidomide Promotes Synergistic Myeloma-Specific Immunity after ASCT
Presented by: Simone A. Minnie, Ph.D., Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Abstract #: 154087

Preclinical data demonstrating the efficacy of a mouse surrogate EOS-448 as a single agent and in combination with an immunomodulatory imide drug (IMiD) in a preclinical model of multiple myeloma was presented by our collaborator at the Fred Hutchinson Cancer Research Center. The Fc-enabled anti-TIGIT monoclonal antibody elicited effective control of multiple myeloma disease progression, while an Fc-disabled version was inactive, indicating the importance of engaging the FcγR. Furthermore, the Fc-enabled anti-TIGIT antibody demonstrated synergistic activity when combined with an IMiD, a class of drugs that has previously shown clinical activity in multiple myeloma.

TIG-007: Study of EOS884448/GSK4428859A Alone, and in Combination with Iberdomide with or without Dexamethasone, in Participants with Relapsed or Refractory Multiple Myeloma
Presented by: Philippe Moreau, M.D., Hematology Department, Nantes University Hospital, Nantes, France
Abstract #: 152395

The presentation highlighted TIG-007, an ongoing open-label, multicenter, dose-escalation/expansion Phase 1/2 trial evaluating the safety, tolerability, and preliminary activity of EOS-448 as monotherapy and in combination with Bristol Myers Squibb’s IMiD, iberdomide, with or without dexamethasone, in adults with relapsed or refractory multiple myeloma. The preclinical data presented from the preclinical model of multiple myeloma provide a strong rationale for combining TIGIT inhibition with immunomodulatory drugs to prevent the progression of myeloma, and previous studies have shown notable clinical activity and acceptable tolerability with iberdomide in combination with dexamethasone or other antimyeloma agents in heavily pre-treated patients with relapsed or refractory multiple myeloma. The study aims to assess the therapeutic opportunity of EOS-448 alone or in combination with iberdomide, with or without dexamethasone to amplify myeloma-specific T cell anti-tumor responses in patients with difficult-to-treat relapsed or refractory multiple myeloma.

TIGIT Therapies Digital Summit 2021:

Targeting TIGIT: Which cell populations are modulated by FcγR engagement?
Presented by: Gregory Driessens, Ph.D., Senior Director, Project Head, iTeos Therapeutics

The presentation featured both preclinical and clinical evidence for the multifaceted mechanism of action of EOS-448, including activation of T cells, modulation of antigen-presenting cells and depletion of regulatory T cells (Tregs) and terminally exhausted T cells. Preclinical data demonstrated that FcγR engagement activated professional antigen-presenting cells either alone or synergistically with anti-PD1, both in the tumor and within the tumor draining lymph node. This effect was only evident when using a fully functional anti-TIGIT antibody, providing support for the design of EOS-448 as an IgG1 antibody. An update on the pharmacodynamic effect of EOS-448 in the blood of treated patients from the Phase 1 trial showed strong depletion of Tregs, an increase in the CD8/Treg ratio and a transient increase in proliferation (as assessed by the Ki67 marker), in line with previous observations with pembrolizumab.

On December 10, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported the schedule of data presentations at the upcoming 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting and exposition, to be held December 11 – 14, 2021, virtually and also live at the Georgia World Congress Center in Atlanta, Georgia (Press release, TG Therapeutics, DEC 10, 2021, View Source [SID1234596765]).

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ASH Presentation Details:

Oral Presentations:
Oral Presentation Title: The Combination of Umbralisib Plus Ublituximab Is Active in Patients with Relapsed or Refractory Marginal Zone Lymphoma (MZL): Results from the Phase 2 Global Unity-NHL Trial

Session Date/Time: Saturday, December 11, 2021 / 10:00 AM ET
Session Name: 623. Mantle Cell, Follicular, and Other B-Cell Lymphomas: Clinical and Epidemiological: Targeted Therapy in Low Grade Lymphoma
Room: Georgia World Congress Center, A411-A412
Lead Author: Julio Chavez, MD, MS, Moffitt Cancer Center, Tampa, FL
Oral Presentation Title: Efficacy and Safety of Umbralisib, Ublituximab (U2), and U2 Plus Bendamustine in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Session Date/Time: Sunday, December 12, 2021 / 5:30 PM ET
Session Name: 626. Aggressive Lymphomas Prospective Therapeutic Trials: Novel Agents and Combinations
Room: Georgia World Congress Center, Thomas Murphy Ballroom 1-2
Lead Author: John Burke, MD, Rocky Mountain Cancer Centers / US Oncology Research, Aurora, CO
Oral Presentation Title: A Phase 2 Study Evaluating the Addition of Ublituximab and Umbralisib (U2) to Ibrutinib in Patients with Chronic Lymphocytic Leukemia (CLL): A Minimal Residual Disease (MRD)-Driven, Time-Limited Approach

Session Date/Time: Sunday, December 12, 2021 / 10:30 AM ET
Session Name: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological I
Room: Georgia World Congress Center, B401-B402
Lead Author: Lindsey E. Roeker, MD, CLL Program, Leukemia Service, Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY
Poster Presentations:
Poster Presentation Title: The Selective Bruton Tyrosine Kinase (BTK) Inhibitor TG-1701 As Monotherapy and in Combination with Ublituximab and Umbralisib (U2) in Patients with B-Cell Malignancies

Date/Time: Saturday, December 11, 2021 / 5:30 PM – 7:30 PM ET
Session Name: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I
Location: Georgia World Congress Center, Hall B5
Lead Author: Chan Y. Cheah, MBBS, DMSc, Linear Clinical Research, Nedlands, Australia; Medical School, University of Western Australia, Perth, Australia; and Department of Haematology, Sir Charles Gairdner Hospital, Perth, Australia
Poster Presentation Title: Favorable Outcomes for Patients Treated with U2 with Co-Morbidities or Concomitant Medications: A Retrospective Analysis of Unity-CLL Phase 3 Trial

Date: Monday, December 13, 2021 / 6:00 PM – 8:00 PM
Session Name: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III
Location: Georgia World Congress Center, Hall B5
Lead Author: Javier Pinilla-Ibarz, MD, Lymphoma Section Head, Director of Immunotherapy, Malignant Hematology Division at the H. Lee Moffitt Cancer Center in Tampa, Florida
Poster Presentation Title: Efficacy and Safety of Ublituximab in Combination with Umbralisib (U2) in Patients with Chronic Lymphocytic Leukemia (CLL) By Treatment Status: A Sub-Analysis of the Phase 3 Unity-CLL Study

Date/Time: Monday, December 13, 2021 / 6:00 PM – 8:00 PM
Session Name: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III
Location: Georgia World Congress Center, Hall B5
Lead Author: Ryan Jacobs, MD, Department of Hematology, Lymphoma Division, Assistant Professor of Medicine, Levine Cancer Institute/Atrium Health, Charlotte, NC
Abstracts are now publicly available via the ASH (Free ASH Whitepaper) meeting website at www.hematology.org. Final presentations will be accessible at the above dates/times via the publications page of TG corporate website at View Source

On December 10, 2021 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported that the company has entered into a clinical trial collaboration agreement with AbbVie, Inc. to evaluate nirogacestat, SpringWorks’ investigational gamma secretase inhibitor, in combination with ABBV-383, AbbVie’s investigational CD3 bispecific antibody directed against B-cell maturation agent (BCMA), in patients with relapsed or refractory multiple myeloma (Press release, SpringWorks Therapeutics, DEC 10, 2021, View Source [SID1234596764]).

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Gamma secretase inhibition helps prevent the cleavage and shedding of BCMA from the surface of myeloma cells. In preclinical models, nirogacestat has been shown to increase levels of membrane-bound BCMA and reduce levels of soluble BCMA, thereby helping to enhance the activity of BCMA-targeted therapies, including CD3 bispecific antibodies.1,2

"We continue to progress our strategy to evaluate nirogacestat in combination with BCMA therapies for patients with multiple myeloma and are delighted to enter into our seventh BCMA clinical collaboration. We look forward to working with AbbVie to study nirogacestat in combination with ABBV-383," said Saqib Islam, Chief Executive Officer of SpringWorks. "Together with our industry-leading collaborators, our goal remains to meaningfully improve clinical outcomes for patients with multiple myeloma."

Under the terms of the agreement, AbbVie will sponsor and conduct the Phase 1b study to evaluate the safety, tolerability, and preliminary efficacy of the combination in patients with relapsed or refractory multiple myeloma, and will assume all costs associated with the study, other than expenses related to the manufacturing of nirogacestat and certain expenses related to intellectual property rights. AbbVie and SpringWorks will also form a joint steering committee to manage the clinical study, which is expected to commence in the first half of 2022.

About Nirogacestat

Nirogacestat is an investigational, oral, selective, small molecule gamma secretase inhibitor in Phase 3 clinical development for desmoid tumors, which are rare and often debilitating and disfiguring soft-tissue tumors. Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which is believed to play a role in activating pathways that contribute to desmoid tumor growth.

In addition, gamma secretase has been shown to directly cleave membrane-bound BCMA, resulting in the release of the BCMA extracellular domain, or ECD, from the cell surface. By inhibiting gamma secretase, membrane-bound BCMA can be preserved, increasing target density while reducing levels of soluble BCMA ECD, which may serve as decoy receptors for BCMA-directed therapies. Nirogacestat’s ability to enhance the activity of BCMA-directed therapies has been observed in preclinical models of multiple myeloma.1,2 SpringWorks is evaluating nirogacestat as a BCMA potentiator and has seven collaborations with industry-leading BCMA developers to evaluate nirogacestat in combinations across modalities, including with an antibody-drug conjugate, two CAR T cell therapies, three bispecific antibodies and a monoclonal antibody. SpringWorks has also formed research collaborations with Fred Hutchinson Cancer Research Center and Dana-Farber Cancer Institute to further characterize the ability of nirogacestat to modulate BCMA and potentiate BCMA-directed therapies using a variety of preclinical multiple myeloma models.

Nirogacestat has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of desmoid tumors and from the European Commission for the treatment of soft tissue sarcoma. The FDA also granted Fast Track and Breakthrough Therapy Designations for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis.

On December 10, 2021 Pfizer Inc. (NYSE: PFE) reported that its board of directors declared an increase in the quarterly cash dividend on the company’s common stock to $0.40 for the first-quarter 2022 dividend, payable March 4, 2022, to holders of the Common Stock of record at the close of business on January 28, 2022 (Press release, Pfizer, DEC 10, 2021, View Source [SID1234596762]). The first-quarter 2022 cash dividend will be the 333rd consecutive quarterly dividend paid by Pfizer.

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"The increase in dividend is a direct reflection of our strong financial performance and continued confidence in our current product portfolio and R&D pipeline," said Dr. Albert Bourla, Pfizer Chairman and Chief Executive Officer.

On December 10, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported a positive interim safety update from the investigator-sponsored, phase 2 IRENE trial in a poster presentation at the 2021 San Antonio Breast Cancer Symposium (SABCS) (Press release, Oncolytics Biotech, DEC 10, 2021, View Source [SID1234596760]).

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The IRENE trial is designed to evaluate the safety and efficacy of pelareorep in combination with Incyte’s anti-PD-1 checkpoint inhibitor retifanlimab for second- or third-line treatment of patients with metastatic triple-negative breast cancer (TNBC). Safety data from the trial show that the combination has been well-tolerated, as no safety concerns have been noted in any of the five patients enrolled in the trial at the time of reporting. The trial remains ongoing and will continue to enroll patients at the Rutgers Cancer Institute of New Jersey and the Ohio State University Comprehensive Cancer Center.

Mridula George, M.D., Medical Oncologist, Rutgers Cancer Institute of New Jersey, Assistant Professor of Medicine, Rutgers Robert Wood Johnson Medical School, and principal investigator of the trial commented, "Checkpoint inhibitors benefit only a minority of TNBC patients due to immunosuppressive tumor microenvironments (TMEs) and poor PD-L1 expression. Prior clinical studies have shown that pelareorep upregulates tumor PD-L1 expression and reverses immunosuppressive TMEs. These findings suggest that pelareorep can address a pressing unmet need in TNBC by synergizing with PD-1 inhibition to increase the proportion of patients responding to therapy. We look forward to evaluating this hypothesis through the IRENE study’s continued advancement and are pleased that the pelareorep-retifanlimab combination has been well-tolerated in each of the patients enrolled in the trial."

In addition to evaluating the safety and efficacy of pelareorep plus retifanlimab, IRENE is also designed to assess changes in PD-L1 expression and correlations between treatment outcomes and changes in peripheral blood T cell populations. This could provide a potential biomarker of pelareorep response that may enable the success of future registrational trials by allowing for the early identification of patients most likely to respond to therapy.

A copy of the SABCS poster titled, "IRENE study: Phase 2 study of Retifanlimab and the oncolytic virus pelareorep in metastatic triple negative breast cancer," will be available on the Posters & Publications page of Oncolytics’ website (LINK) following the conclusion of the symposium.

About IRENE
The IRENE (INCMGA00012 and the oncolytic virus pelareorep in metastatic triple-negative breast cancer) study is a single-arm, open-label, phase 2 study evaluating the combination of pelareorep and Incyte’s anti-PD-1 checkpoint inhibitor retifanlimab (INCMGA00012) for the second- or third-line treatment of unresectable locally advanced or metastatic triple-negative breast cancer. The study will enroll 25 patients and is being conducted at the Rutgers Cancer Institute of New Jersey and The Ohio State University Comprehensive Cancer Center.

Study participants will receive pelareorep intravenously on days 1, 2, 15, and 16 of 28-day treatment cycles. Retifanlimab will be administered on day 3 of each cycle, with treatment cycles continuing until disease progression is observed. The co-primary endpoints of the study are safety and objective response rate. Secondary endpoints include progression-free survival, overall survival, and duration of response. Exploratory endpoints include peripheral T cell clonality and pre- vs. post-treatment change in tumor PD-L1 expression.

For more information on the IRENE study, refer to View Source