On October 1, 2021 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported five poster presentations at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), being held in Washington, D.C., and virtually November 10-14, 2021 (Press release, Xencor, OCT 1, 2021, View Source [SID1234590660]).

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The presentations will include updated clinical results from expansion cohorts in the Phase 1 study of vudalimab (XmAb717), a selective PD-1 x CTLA-4 bispecific antibody, in patients with prostate cancer, renal cell carcinoma and other cancers without approved checkpoint therapies. New data from four preclinical-stage programs, including Xencor’s IL-12-Fc cytokine program, PD-L1 x CD28 bispecific antibody program, TGFβR2 bispecific antibody platform, and bispecific NK cell engager platform, will also be presented.

Presentation Details

Abstract 523, "Preliminary clinical experience with XmAb20717, a PD-1 x CTLA-4 bispecific antibody, in patients with advanced solid tumors"
Abstract 707, "IL12 Fc-fusions engineered for reduced potency and extended half-life exhibit strong anti-tumor activity and improved therapeutic index compared to wild-type IL12 agents"
Abstract 698, "PD-L1 targeted CD28 costimulatory bispecific antibodies enhance T cell activation in solid tumors"
Abstract 872, "PD1 x TGFbR2 and CD5 x TGFbR2 bispecifics selectively block TGFbR2 on target-positive T cells, promote T cell activation, and elicit an anti-tumor response in solid tumors"
Abstract 787, "Natural Killer cell engagers activate innate and adaptive immunity and show synergy with proinflammatory cytokines"
Posters will be available in the poster hall and virtually to registrants of the SITC (Free SITC Whitepaper) Annual Meeting, beginning at 7:00 a.m. ET on Friday, November 12. In the poster hall, odd numbered posters will be displayed on Friday, November 12, and even numbered posters will be displayed on Saturday, November 13. Posters will be archived under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com.

About Vudalimab (XmAb717)

Vudalimab (XmAb717) is an XmAb bispecific antibody that simultaneously targets immune checkpoint receptors PD-1 and CTLA-4 and is designed to promote tumor-selective T-cell activation. Xencor’s approach to dual checkpoint/co-stimulation reduces the need for the multiple antibodies and allows for more selective targeting of T cells with high checkpoint expression, which may potentially improve the therapeutic index of combination immunotherapies. In preclinical studies, dual blockade of PD-1 and CTLA-4 with vudalimab significantly enhanced T cell proliferation and activation, and anti-tumor activity in vivo. Xencor has initiated a Phase 2 clinical study of vudalimab in patients with metastatic castration resistant prostate cancer (mCRPC), as a monotherapy or in combination depending on subtype, and a Phase 2 clinical study in patients with advanced gynecologic and genitourinary malignancies, as well as high-risk mCRPC.

On October 1, 2021 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported that one oral and four poster presentations for the Company’s induced pluripotent stem cell (iPSC) product platform were accepted for presentation at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) being held November 10-14, 2021 (Press release, Fate Therapeutics, OCT 1, 2021, View Source [SID1234590638]).

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The oral presentation will highlight preclinical data for FT536, the Company’s off-the-shelf, multiplexed-engineered, iPSC-derived, chimeric antigen receptor (CAR) NK cell product candidate that uniquely targets the α3 domain of the MHC class I related proteins A (MICA) and B (MICB). In a recent publication in Cancer Immunology Research (DOI: 10.1158/2326-6066.CIR-19-0483), Kai W. Wucherpfennig, M.D., Ph.D., Chair of the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute and co-leader of the Cancer Immunology Program at Dana-Farber / Harvard Cancer Center, demonstrated that cancers with loss of MHC Class I expression can be effectively targeted with MICA/B α3 domain-specific antibodies to restore NK cell-mediated immunity against solid tumors. The FT536 program is supported by an exclusive license from the Dana-Farber Cancer Institute to intellectual property covering novel antibody fragments binding MICA/B for iPSC-derived cellular therapeutics. The Company expects to submit an Investigational New Drug (IND) application for FT536 in the fourth quarter of 2021 for the treatment of advanced solid tumors, including in combination with monoclonal antibody therapy.

Poster presentations at SITC (Free SITC Whitepaper) will include preclinical data on new functional elements that the Company is evaluating for incorporation into its iPSC-derived cell product candidates for solid tumors. These synthetic features include engineered chemokine receptors, which the Company has demonstrated can enhance the trafficking and homing of iPSC-derived CAR T cells to tumors, and synthetic TGFβ re-direct receptors, which the Company has shown can exploit immuno-suppressive cytokines found in the tumor microenvironment to potentiate iPSC-derived CAR T cells and improve anti-tumor activity.

Oral Presentation

FT536 Path to IND: Ubiquitous targeting of solid tumors with an off-the-shelf, first-of-kind MICA/B-specific CAR-iNK cellular immunotherapy
Abstract #: 117
Session 212: Cellular Therapies; November 13, 3:40 pm – 4:55 pm EST
Poster Presentation

Synthetic re-direction of TGFβ receptors as a novel strategy to enhance the anti-tumor activity of iPSC-derived CAR-T cells in solid tumors
Abstract #: 138
Chemokine receptor engineering enhances trafficking and homing of primary and iPSC-derived CAR-T cells to solid tumors
Abstract #: 120
Off-the-shelf, engineered iPSC-derived NK cells mediate potent cytotoxic activity against primary glioblastoma cells and promote durable long-term survival in vivo
Abstract #: 169
Novel FcyR recombinant fusion facilitates antibody arming of engineered iPSC-derived NK cells to enhance targeting and killing of ovarian cancer cells
Abstract #: 197
About MICA and MICB Proteins
The major histocompatibility complex (MHC) class I related proteins A (MICA) and B (MICB) are induced by cellular stress, damage or transformation, and the expression of MICA and MICB proteins has been reported for many tumor types. Cytotoxic lymphocytes, such as NK cells and CD8+ T cells, can detect and bind the membrane-distal α1 and α2 domains of MICA/B, activating a potent cytotoxic response. However, cancer cells frequently evade immune cell recognition by proteolytic shedding of the α1 and α2 domains of MICA/B. The clinical importance of proteolytic shedding is reflected in the association of high serum concentrations of shed MICA/B with disease progression in many solid tumors. Several recent publications have shown that therapeutic antibodies targeting the membrane-proximal α3 domain strongly inhibited MICA/B shedding, resulting in a substantial increase in the cell surface density of MICA/B and restoration of NK cell-mediated tumor immunity (DOI:10.1126/science.aao0505). Therapeutic approaches aimed at targeting the α3 domain of MICA/B therefore represent a potentially promising novel strategy to overcome this prominent evasion mechanism as a means of restoring anti-tumor immunity.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

On October 1, 2021 -Asher Biotherapeutics, a biotechnology company developing precisely-targeted immunotherapies for cancer, autoimmune, and infectious diseases, reported that it will present two abstracts at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting (SITC 2021), being held in Washington D.C. and virtually, November 10-14, 2021 (Press release, Asher Biotherapeutics, OCT 1, 2021, View Source [SID1234590661]).

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Collectively, the presentations demonstrate preclinical proof-of-concept for Asher Bio’s cis-targeting approach and lead program AB248. AB248 is an engineered interleukin-2 (IL-2) immunotherapy, designed specifically to target CD8+ effector T cells. Asher expects to file an investigational new drug application for AB248 in the third quarter of 2022.

Details of the presentations are as follows:

Oral Presentation:
Title: CD8-targeted IL-2 drives potent anti-tumor efficacy and promotes action of tumor specific vaccines
Authors: Hussein Sultan, PhD, Kelly Moynihan, PhD, Yuang Song, Ton Schumacher, PhD, Andy Yeung, PhD, Ivana Djuretic, PhD, and Robert D. Schreiber, PhD
Abstract Number: 578
Session: Cellular Therapies, Saturday 11/13/2021, 3:40 pm – 4:55 pm ET

Poster Presentation:
Title: Selective activation of CD8+ T cells by a CD8-targeted IL-2 results in enhanced anti-tumor efficacy and safety
Authors: Kelly Moynihan, PhD, Danielle Pappas, Terrence Park, Wei Chen PhD, Irene Ni, Paul Bessette PhD, Mike Chin, Ton Schumacher, PhD, Andy Yeung, PhD, and Ivana Djuretic, PhD
Abstract Number: 717
Session: Poster Hall E, Friday 11/12/2021, 7:00 am – 8:30 pm ET

Both abstracts will become available online on the SITC (Free SITC Whitepaper) conference website beginning at 8:00 a.m. ET on Tuesday, November 9, 2021.

On October 1, 2021 Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapies company focused on driving innovation to transform outcomes for cancer patients, reported it will present initial data from its ongoing Phase 1 clinical trial of ONCR-177 at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting, taking place November 12–14, 2021 in Washington, D.C. and virtually (Press release, Oncorus, OCT 1, 2021, View Source [SID1234590640]).

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ONCR-177, Oncorus’ lead oncolytic Herpes Simplex Virus (oHSV) product candidate, is an intratumorally (iTu) administered viral immunotherapy being developed for multiple solid tumor indications. The Phase 1 open-label, multi-center, dose escalation and expansion clinical trial is designed to evaluate the safety and tolerability of ONCR-177 alone and in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients with advanced and/or refractory cutaneous, subcutaneous or metastatic nodal solid tumors or with liver metastases of solid tumors.

The details for Oncorus’ SITC (Free SITC Whitepaper) poster are as follows:

Title: Initial results of a Phase 1 study of intratumoral ONCR-177, an oncolytic herpes-simplex virus-1 expressing five immunomodulatory transgenes, in subjects with advanced injectable tumors
Abstract #: 511
Primary Author/Presenter: Jong Chul Park, M.D., Instructor, Medicine, Harvard Medical School and Assistant, Medicine, Massachusetts General Hospital
Date/Time: November 12–14, 2021, 7:00 a.m.– 8:30 p.m. ET
Location: Poster Hall, Walter E. Washington Convention Center, Washington, D.C.

On October 1, 2021 Transgene (Euronext Paris: TNG) (Paris:TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, and BioInvent International AB ("BioInvent") (Nasdaq Stockholm: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, reported that they will present additional preclinical data on their novel dual mechanism-of-action oncolytic vaccinia virus BT-001 at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC2021) in November 2021 (Press release, Transgene, OCT 1, 2021, View Source [SID1234590662]).

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SITC2021 will take place on November 10–14, 2021, at the Walter E. Washington Convention Center in Washington, D.C. and virtually. The poster will be presented on November 13, with the title "Vectorized Treg-depleting aCTLA-4 elicits antigen cross-presentation and CD8+ T cell immunity to reject "cold" tumors". Authors: Monika Semmrich, Jean-Baptiste Marchand, Matilda Rehn, Laetitia Fend, Christelle Remy, Petra Holmkvist, Nathalie Silvestre, Carolin Svensson, Patricia Kleinpeter, Jules Deforges, Fred Junghus, Linda Mårtensson, Johann Foloppe, Ingrid Teige, Eric Quéméneur and Björn Frendéus.

BT-001 is an oncolytic virus generated using Transgene’s Invir.IO platform and its patented large-capacity VVcopTK-RR- oncolytic virus, which has been engineered to encode both a Treg-depleting human recombinant anti-CTLA-4 antibody generated by BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms, and the human GM-CSF cytokine. By selectively targeting the tumor microenvironment, BT-001 is expected to elicit a much stronger and more effective antitumoral response. As a consequence, by reducing systemic exposure, the safety and tolerability profile of the anti-CTLA-4 antibody is expected to be greatly improved.

BT-001 is being co-developed as part of a 50/50 collaboration between BioInvent and Transgene.

Recruitment in the ongoing Phase I/IIa clinical study of BT-001 (NCT04725331) in Europe and the U.S. is progressing well. The trial evaluates BT-001 as a single agent and in combination with pembrolizumab for the treatment of solid tumors.

Initial Phase I data are expected in the first half of 2022.