On October 5, 2022 4D pharma plc (AIM: DDDD) (in administration), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs), a novel class of drug derived from the microbiome, reported that two poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting (SITC 2022), held from November 8-12, 2022 (Press release, 4d Pharma, OCT 5, 2022, View Source [SID1234621708]). The two e-posters will be available from 2.00 pm GMT (9.00 am ET) on November 10, 2022, via the 4D pharma website at www.4dpharmaplc.com.

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"With these two presentations at SITC (Free SITC Whitepaper) 2022, 4D pharma continues to generate clinical data deepening our understanding of the mechanisms driving the activity of MRx0518 to both overcome resistance to checkpoint inhibitors, and act as a monotherapy in the treatment of solid tumors," commented Alex Stevenson, Chief Scientific Officer, 4D pharma. "These data are further evidence of the positive effects of a single strain Live Biotherapeutic on both the human immune system and the microbiome, leading to better treatment outcomes for patients."

Poster presentation details are as follows:

Presentation Title: Combination of MRx0518 and anti-PD-1 overcomes checkpoint inhibitor resistance via myeloid modulation

Presenting Author: Dr. June Li, Research Scientist, Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center

Abstract Number: 838

Presentation Title: Oral administration of MRx0518 in treatment-naïve cancer patients is associated with compositional taxonomic and metabolomic changes indicative of anti-tumorigenic efficacy

Presenting Author: Dr. Mark P. Lythgoe, Academic Clinical Fellow in Medical Oncology and Pharmacist, Imperial College London

Abstract Number: 627

On 24 June 2022, David Pike and James Clark of Interpath Advisory were appointed as administrators of 4D pharma plc. The administrators have had no oversight of or involvement in the preparation of the SITC (Free SITC Whitepaper) 2022 poster presentations nor in any materials which will be circulated in advance of or during SITC (Free SITC Whitepaper) 2022. Therefore, the administrators make no statement or representation in respect of the materials shared or discussed in advance of or during SITC (Free SITC Whitepaper) 2022.

About MRx0518

MRx0518 is single strain Live Biotherapeutic product in development for the treatment of cancer. It is delivered as an oral capsule and stimulates the body’s immune system, directing it to produce cytokines and immune cells that are known to attack tumors. It is currently being evaluated in three clinical trials in cancer patients. MRx0518-I-001 is a neoadjuvant monotherapy study in a variety of solid tumors and is being conducted at Imperial College (London, UK). MRx0518-I-002 is in combination with KEYTRUDA (pembrolizumab) in patients who have previously progressed on anti PD-1 therapies. The Coordinating Investigator of the study is at The University of Texas MD Anderson Cancer Center, Houston, USA, with multiple additional sites in the US. The study is being conducted in collaboration with MSD, the tradename of Merck & Co., Inc., Kenilworth, NJ, USA. MRx0518-I-003 is in combination with preoperative radiotherapy in resectable pancreatic cancer. A fourth clinical trial is planned, in collaboration with Merck KGaA and Pfizer Inc., of BAVENCIO (avelumab) in combination with MRx0518 as a first-line maintenance therapy for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.

On October 5, 2022 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported seven poster presentations at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), being held in Boston, November 10-12, 2022 (Press release, Xencor, OCT 5, 2022, View Source [SID1234621707]).

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Data from the first patients enrolled in a Phase 2 study of vudalimab, Xencor’s selective PD-1 x CTLA-4 bispecific antibody, plus chemotherapy in patients with metastatic castration-resistant prostate cancer, will be presented in abstract 668.

Presentation Details

Clinical Trials in Progress

Abstract 667, "A Phase 1, multiple-dose study to evaluate the safety and tolerability of XmAb819 (ENPP3 x CD3) in subjects with relapsed or refractory clear cell renal cell carcinoma (RCC)"
Abstract 668, "A Phase 2 study of vudalimab, a PD-1 x CTLA-4 bispecific antibody, plus chemotherapy or targeted therapy in patients with molecularly defined subtypes of metastatic castration-resistant prostate cancer"
Abstract 733, "A Phase 2 study of vudalimab (XmAb20717), an anti-PD-1/CTLA-4 bispecific antibody, in patients with selected gynecological malignancies and high-risk metastatic castration-resistant prostate-cancer"
Preclinical Programs

Abstract 1067, "Synergistic combination of Natural Killer cell engagers (NKEs) with proinflammatory cytokines"
Abstract 1073, "Costimulatory CD28 trispecific antibodies targeting PDL1 and PDL2 enhance T cell activation in solid tumors"
Abstract 1079, "LAG3-targeted IL15/IL15Rα-Fc (LAG3 x IL15) fusion proteins for preferential TIL expansion via cis delivery of IL15 to LAG3+ cells"
Abstract 1372, "XmAb143, an engineered IL18 heterodimeric Fc-fusion, features improved stability, reduced potency, and insensitivity to IL18BP"
Posters will be available in the poster hall and virtually to registrants of the SITC (Free SITC Whitepaper) Annual Meeting, beginning at 9:00 a.m. ET on Thursday, November 10. In the poster hall, odd numbered posters will be displayed on Thursday, November 10, and even numbered posters will be displayed on Friday, November 11. Posters will be archived under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com.

About Vudalimab

Vudalimab 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 inhibition reduces the need for multiple antibodies and allows for more selective targeting of T cells with high checkpoint expression of both targets, 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 is conducting a Phase 2 clinical study of vudalimab in patients with metastatic castration resistant prostate cancer (mCRPC), plus chemotherapy for certain patient populations, and a Phase 2 clinical study in patients with advanced gynecologic and genitourinary malignancies, as well as high-risk mCRPC.

About XmAb819

XmAb819 is a tumor-targeted, T-cell engaging XmAb 2+1 bispecific antibody in development for patients with renal cell carcinoma (RCC). XmAb819 engages the immune system by activating T cells for highly potent and targeted killing of tumor cells expressing ENPP3, an antigen highly expressed on kidney cancers. ENPP3 is differentially expressed between RCC (high expression) and normal tissues (low expression). To attack RCC cells selectively, XmAb819 was engineered as an XmAb 2+1 bispecific antibody with two binding domains against ENPP3 and one cytotoxic T-cell binding domain against CD3, a component of the T-cell receptor (TCR) complex. Xencor’s XmAb Bispecific Fc Domain serves as the scaffold for these binding domains and provides long circulating half-life, stability and ease of manufacture. Xencor is conducting a Phase 1 study of XmAb819 in patients with advanced renal cell carcinoma.

On October 5, 2022 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported seven poster presentations at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), being held in Boston, November 10-12, 2022 (Press release, Xencor, OCT 5, 2022, View Source [SID1234621707]).

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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

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Data from the first patients enrolled in a Phase 2 study of vudalimab, Xencor’s selective PD-1 x CTLA-4 bispecific antibody, plus chemotherapy in patients with metastatic castration-resistant prostate cancer, will be presented in abstract 668.

Presentation Details

Clinical Trials in Progress

Abstract 667, "A Phase 1, multiple-dose study to evaluate the safety and tolerability of XmAb819 (ENPP3 x CD3) in subjects with relapsed or refractory clear cell renal cell carcinoma (RCC)"
Abstract 668, "A Phase 2 study of vudalimab, a PD-1 x CTLA-4 bispecific antibody, plus chemotherapy or targeted therapy in patients with molecularly defined subtypes of metastatic castration-resistant prostate cancer"
Abstract 733, "A Phase 2 study of vudalimab (XmAb20717), an anti-PD-1/CTLA-4 bispecific antibody, in patients with selected gynecological malignancies and high-risk metastatic castration-resistant prostate-cancer"
Preclinical Programs

Abstract 1067, "Synergistic combination of Natural Killer cell engagers (NKEs) with proinflammatory cytokines"
Abstract 1073, "Costimulatory CD28 trispecific antibodies targeting PDL1 and PDL2 enhance T cell activation in solid tumors"
Abstract 1079, "LAG3-targeted IL15/IL15Rα-Fc (LAG3 x IL15) fusion proteins for preferential TIL expansion via cis delivery of IL15 to LAG3+ cells"
Abstract 1372, "XmAb143, an engineered IL18 heterodimeric Fc-fusion, features improved stability, reduced potency, and insensitivity to IL18BP"
Posters will be available in the poster hall and virtually to registrants of the SITC (Free SITC Whitepaper) Annual Meeting, beginning at 9:00 a.m. ET on Thursday, November 10. In the poster hall, odd numbered posters will be displayed on Thursday, November 10, and even numbered posters will be displayed on Friday, November 11. Posters will be archived under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com.

About Vudalimab

Vudalimab 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 inhibition reduces the need for multiple antibodies and allows for more selective targeting of T cells with high checkpoint expression of both targets, 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 is conducting a Phase 2 clinical study of vudalimab in patients with metastatic castration resistant prostate cancer (mCRPC), plus chemotherapy for certain patient populations, and a Phase 2 clinical study in patients with advanced gynecologic and genitourinary malignancies, as well as high-risk mCRPC.

About XmAb819

XmAb819 is a tumor-targeted, T-cell engaging XmAb 2+1 bispecific antibody in development for patients with renal cell carcinoma (RCC). XmAb819 engages the immune system by activating T cells for highly potent and targeted killing of tumor cells expressing ENPP3, an antigen highly expressed on kidney cancers. ENPP3 is differentially expressed between RCC (high expression) and normal tissues (low expression). To attack RCC cells selectively, XmAb819 was engineered as an XmAb 2+1 bispecific antibody with two binding domains against ENPP3 and one cytotoxic T-cell binding domain against CD3, a component of the T-cell receptor (TCR) complex. Xencor’s XmAb Bispecific Fc Domain serves as the scaffold for these binding domains and provides long circulating half-life, stability and ease of manufacture. Xencor is conducting a Phase 1 study of XmAb819 in patients with advanced renal cell carcinoma.

On October 5, 2022 GSK plc (LSE/NYSE: GSK) reported positive headline results of the PERLA phase II trial, which met its primary endpoint of objective response rate (ORR) by Response Evaluation Criteria in Solid Tumours (RECIST) criteria as determined by blinded independent central review (Press release, GlaxoSmithKline, OCT 5, 2022, View Source [SID1234621706]). The trial evaluated dostarlimab in combination with chemotherapy versus pembrolizumab in combination with chemotherapy in first-line patients with metastatic non-squamous non-small cell lung cancer (NSCLC). The PERLA phase II trial is a randomised, double-blind trial of 243 patients and is the largest global head-to-head trial of programmed death receptor-1 (PD-1) inhibitors in this population.The trial was not designed to demonstrate superiority.

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Full results from the PERLA phase II trial, including the primary endpoint of ORR and the key secondary endpoint of progression-free survival, with results by programmed death ligand-1 (PD-L1) expression subgroups, will be presented at an upcoming scientific meeting.

The safety and tolerability profile of dostarlimab in the PERLA phase II trial was consistent with previous clinical trials of similar regimens. The most common treatment-emergent adverse reactions were anaemia, asthenia, nausea, constipation, cough, dyspnoea, vomiting, decreased appetite, and neutropenia.

In addition, GSK is also advancing both arms of the COSTAR Lung trial into phase III. The decision follows the recommendation of the Independent Data Monitoring Committee, given that the trial met its pre-specified expansion criteria per protocol. The COSTAR Lung phase III trial is a randomized, open label 3-arm trial comparing cobolimab, an investigational selective anti–TIM-3 monoclonal antibody, plus dostarlimab plus docetaxel to dostarlimab plus docetaxel to docetaxel alone in patients with advanced NSCLC who have progressed on prior anti-PD-L1 therapy and chemotherapy.

Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK said: "These trials support the ambition for dostarlimab to become the backbone of our ongoing immuno-oncology-based research and development programme when used alone and in combination with standard of care and future novel cancer therapies, particularly in patients with currently limited treatment options."

About PERLA

The PERLA phase II trial is a global, randomised, double-blind trial of 243 patients evaluating the efficacy and safety of dostarlimab plus chemotherapy compared to pembrolizumab plus chemotherapy in patients with metastatic non-squamous NSCLC without a known sensitising epidermal growth factor receptor, anaplastic lymphoma kinase, or receptor tyrosine kinase-1 mutation, V600E mutation of the BRAF gene or other genomic mutation for which an approved targeted therapy is available. The primary endpoint was objective response rate of dostarlimab plus chemotherapy versus pembrolizumab plus chemotherapy assessed by blinded independent central review per RECIST v1.1. Secondary endpoints include investigator-assessed progression-free survival per RECIST v1.1, overall survival, and safety.

About COSTAR Lung

The COSTAR Lung trial is a phase II/III global, randomized, open-label trial of 750 patients. The study evaluates the efficacy and safety of cobolimab plus dostarlimab plus docetaxel and dostarlimab plus docetaxel compared to docetaxel in patients with advanced non-squamous and squamous NSCLC whose disease had progressed on prior therapy with an anti-PD-(L)1 agent and a platinum doublet-based chemotherapy given in combination or in sequence. The study does not include patients with a known sensitizing epidermal growth factor receptor, anaplastic lymphoma kinase, or receptor tyrosine kinase-1 mutation, for which an approved targeted therapy is available. The primary endpoint is overall survival.

About Jemperli (dostarlimab)

Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2. Jemperli is being investigated in registrational enabling studies, as monotherapy and as part of combination regimens, including in women with recurrent or primary advanced endometrial cancer, women with stage III or IV non-mucinous epithelial ovarian cancer, and in patients with other advanced solid tumours or metastatic cancers. Jemperli is not approved anywhere in the world in combination with chemotherapy in first-line patients with metastatic non-squamous NSCLC or in combination with other agents to treat patients with advanced NSCLC who have progressed on prior anti-PD-L1 therapy and chemotherapy.

Jemperli was discovered by AnaptysBio and licensed to TESARO, Inc., under a Collaboration and Exclusive License Agreement signed in March 2014. The collaboration has resulted in three monospecific antibody therapies that have progressed into the clinic. These are: Jemperli (GSK4057190), a PD-1 antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialization, and manufacturing of each of these Products under the Agreement.

About Cobolimab

Cobolimab is a monoclonal antibody against the inhibitory T-cell receptor, T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), with potential immune checkpoint inhibitory and antineoplastic activities. Cobolimab was discovered by AnaptysBio and TESARO, Inc., under a Collaboration and Exclusive License Agreement signed in March 2014. The collaboration has resulted in three monospecific antibody drugs that have progressed into the clinic. These are: dostarlimab (GSK4057190), a PD-1 antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialisation, and manufacture of each of these products under the Agreement.

Important Information for Jemperli in the EU

Indication

Jemperli is indicated as monotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability‑high (MSI‑H) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum‑containing regimen.

On October 5, 2022 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported that the Company will present clinical and preclinical data for the Company’s induced pluripotent stem cell (iPSC) product platform at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting being held in Boston, MA, and virtually, November 8-12, 2022 (Press release, Fate Therapeutics, OCT 5, 2022, View Source [SID1234621705]). Details of the SITC (Free SITC Whitepaper) poster presentations are as follows:

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Clinical Programs

Combining FT536, a pan-tumor targeting CAR NK cell therapy, with CD16 engagers provides a coordinated targeting strategy to overcome tumor heterogeneity

Interim Phase I clinical data of FT538, an off-the-shelf, multiplexed-engineered, iPSC-derived NK cell therapy, combined with monoclonal antibodies in patients with advanced solid tumors

Phase I results of FT516, an off-the-shelf, iPSC-derived NK cell therapy expressing a high-affinity, non-cleavable CD16 (hnCD16) combined with avelumab in patients with advanced solid tumors

Results of a Phase I trial of FT500, a first-in-class, off-the-shelf, iPSC‑derived NK cell therapy combined with PD-1/PD-L1 checkpoint blockade therapy and IL-2 in patients with advanced solid tumors

Preclinical Programs

Targeting cold tumors using iPSC-derived CAR-T cells directed to the immune checkpoint molecule and tumor-associated antigen B7-H3

Off-the-shelf iPSC-derived CAR-T cells targeting KLK2 demonstrate prolonged tumor control and survival in xenograft models of prostate cancer

Off-the-shelf iPSC-derived CAR-T cells containing seven functional edits overcome antigen heterogeneity, improve trafficking and withstand immunosuppression associated with failed tumor treatment

iPSC Product Platform

Engineering of synthetic chemokine receptors into iPSC-derived CAR-T cells to increase homing and enhance trafficking into solid tumors

iPSC-derived NK cells engineered with a novel TGFβ signal redirector receptor exhibit enhanced performance against solid tumors

Tri-modal CAR+TCR+hnCD16+ iPSC-derived T cells co-targeting surface and intracellular/neoantigens demonstrate additive effect on overcoming tumor heterogeneity and cancer escape

Novel immune reconstitution model highlights the importance of stealth strategies that potentiate effector cell function and promote functional persistence of next-generation adoptive cell therapies

Preclinical in vivo model development: Highlighting success and discussing xenograft advancements, a step closer in predicting patient outcomes

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 are designed to 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 designed to overcome 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.