On November 4, 2021 MorphoSys AG (FSE: MOR; NASDAQ: MOR) reported that new data on approved and clinical-stage therapeutics will be presented during the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from December 11-14 in Atlanta, Georgia United States (Press release, MorphoSys, NOV 4, 2021, View Source [SID1234594369]). Ten abstracts were accepted, including two oral presentations, from the comprehensive MorphoSys portfolio, including abstracts for the BET inhibitor pelabresib, which MorphoSys added to its pipeline through the acquisition of Constellation Pharmaceuticals.

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"MorphoSys continues to contribute significantly to scientific advances in hematology-oncology with our cancer immunotherapy and our expanded portfolio including the development of epigenetic modifiers," said Malte Peters, MD, MorphoSys Chief Research and Development Officer. "The important data published in our ASH (Free ASH Whitepaper) presentations show our commitment to finding cures that redefine how cancer is treated."

The MANIFEST and RE-MIND2 presentations at ASH (Free ASH Whitepaper) 2021 are the culmination of a transformational year for MorphoSys. Through groundbreaking proprietary research in immunotherapy and the addition of Constellation Pharmaceuticals’ high-potential product candidates, MorphoSys has bolstered its position as an emerging leader in hematology-oncology.

Highlights of presentations from the MorphoSys hematology-oncology portfolio include:

– An update of clinical and translational data from the ongoing MANIFEST trial for JAK naïve patients treated with pelabresib (CPI-0610) in combination with ruxolitinib (study arm 3), representing the analysis for the primary endpoint SVR35

– An update of clinical and translational data from the ongoing MANIFEST trial for pelabresib (CPI-0610) monotherapy in patients with myelofibrosis

– Expanded Real-World RE-MIND2 dataset comparing tafasitamab and lenalidomide (Tafa+Len) outcomes to those observed in matched cohorts of 1) polatuzumab vedotin plus bendamustine and rituximab (pola-BR), 2) rituximab plus lenalidomide (R2); and 3) CAR-T therapies

Follow MorphoSys on Twitter via @MorphoSys and visit the MorphoSys ASH (Free ASH Whitepaper) virtual booth at www.MorphoSysEvents.com

PELABRESIB ASH (Free ASH Whitepaper) 2021 ACCEPTED ABSTRACTS

Study Abstract Title Authors Status / Publication # /
Session
MANIFEST​ Pelabresib (CPI-0610) Monotherapy in Patients with Myelofibrosis – Update of Clinical and Translational Data from the Ongoing MANIFEST Trial ​ Marina Kremyanskaya, John Mascarenhas, Francesca Palandri, Alessandro M. Vannucchi, Srdan Verstovsek, Claire Harrison, Prithviraj Bose, Gary J. Schiller, Raajit K. Rampal, Mark W. Drummond, Vikas Gupta, Andrea Patriarca, Nikki Granacher, Joseph Scandura, Witold Prejzner, Lino Teichmann, Natalia Curto-García, Ronald Hoffman, Gozde Colak, Zheng Ren, Suresh Bobba, Jike Cui, Sergey Efuni, Moshe Talpaz​ Oral Presentation
#141​
Session Name: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Non-JAK inhibitor Therapies for Myelofibrosis ​
Session Date: Saturday, December 11, 2021 ​
Session Time: 12:00 PM – 1:30 PM ​
Presentation Time: 12:30 PM ​
Room: Georgia World Congress Center, A411-A412​
Pelabresib Ph1 ​ PK and PD Assessment of BET Inhibitor Pelabresib (CPI-0610) in Patients With Relapsed or Refractory Lymphoma: Findings from a Phase 1 Study​ Kristie A. Blum, Jeffrey Supko, Michael Maris, Ian Flinn, Andre Goy, Anas Younes, Suresh Bobba, Adrian Senderowicz, Sergey Efuni, Ronda Rippley, Jeremy S. Abramson​ POSTER
#​1202
Session Name: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster I
Date: Saturday, December 11, 2021 ​
Presentation Time: 5:30 PM – 7:30 PM ​
Location: Georgia World Congress Center, Hall B5​​
MANIFEST​ Disease-Modifying Potential of BET Inhibitor Pelabresib (CPI-0610) as Demonstrated by Improvements in Bone Marrow Function and Clinical Activity in Patients With Myelofibrosis – Preliminary Data ​ Srdan Verstovsek, Mohamed E. Salama, John Mascarenhas, Moshe Talpaz, Ruben Mesa, Alessandro M. Vannucchi, Raajit K. Rampal, Stephen Oh, Horatiu Olteanu, April Chiu, Dong Chen, Curtis A Hanson, Natalia Curto-García, Pietro Taverna, Jike Cui, Oksana Zavidij, Zehua Chen, Gozde Colak, Sergey Efuni, Patricia Keller, Patrick Trojer, Claire Harrison​ Accepted as poster
#2568​
Session Name: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster II ​
Date: Sunday, December 12, 2021 ​
Presentation Time: 6:00 PM – 8:00 PM ​
Location: Georgia World Congress Center, Hall B5​

TAFASITAMAB ASH (Free ASH Whitepaper) 2021 ACCEPTED ABSTRACTS

Study Abstract Title Authors Status / Publication # /
Session
RE-MIND2 Tafasitamab plus Lenalidomide versus pola-BR, R2, and CAR T: Comparing Outcomes from RE-MIND2, an Observational, Retrospective Cohort Study in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Grzegorz S. Nowakowski, Dok Hyun Yoon, Patrizia Mondello, Erel Joffe, Anthea Peters, Isabelle Fleury, Richard Greil, Matthew Ku, Reinhard Marks, Kibum Kim, Pier Luigi Zinzani, Judith Trotman, Lorenzo Sabatelli, Dan Huang, Eva E. Waltl, Mark Winderlich, Sumeet Ambarkhane, Nuwan C. Kurukulasuriya, Raul Cordoba, Georg Hess, Gilles Salles Accepted as oral presentation
#183
Session Name: 905. Outcomes Research-Lymphoid Malignancies: Lymphoma/CLL Real-World Data
Session Date: Saturday, December 11, 2021
Session Time: 12:00 PM – 1:30 PM
Presentation Time: 12:30 PM
Room: Georgia World Congress Center, Sidney Marcus Auditorium
Shared Decision Making in R/R DLBCL Preferences and Perceptions Regarding Treatment Decision-Making For Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL) Mallory Yung, Frederick Schnell, Mirko Vukcevic, Nuwan C. Kurukulasuriya Accepted as poster (collaboration with Avalere) #1928
Session Name: 902. Health Services Research-Lymphoid Malignancies: Poster I
Date: Saturday, December 11, 2021
Presentation Time: 5:30 PM – 7:30 PM
Location: Georgia World Congress Center, Hall B5
inMIND (Incyte) inMIND: A Phase 3 Study of Tafasitamab Plus Lenalidomide and Rituximab Versus Placebo Plus Lenalidomide and Rituximab for Relapsed/Refractory Follicular or Marginal Zone Lymphoma Sehn L, Luminari S, Salar A, Wahlin B, Gopal A, Bonnet C, Paneesha S, Trneny M, Manzke O, Seguy F, Li D, Hubel K, Scholz C Accepted as poster
Session Name: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II
Date: Sunday, December 12, 2021
Presentation Time: 6:00 PM – 8:00 PM
Tafasitamab + TAK981 preclinical The SUMOylation Inhibitor TAK-981 in Combination with the CD19-Targeting Antibody Tafasitamab Shows Enhanced Anti-Tumor Activity in Preclinical B-Cell Lymphoma Models Maria Patra-Kneuer, Akito Nakamura, Keli Song, Stephen Grossman, Andrea Polzer, Carmen Ginzel, Stefan Steidl, Allison J Berger, Igor Proscurshim, Christina Heitmüller Accepted as poster
#2268
Session Name: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II
Date: Sunday, December 12, 2021
Presentation Time: 6:00 PM – 8:00 PM
Location: Georgia World Congress Center, Hall B5
Tafasitamab + CAR-T preclinical The Impact of Prior Treatment with a CD19 Targeting Monoclonal Antibody on Subsequent Treatment with CD19 Targeting CART Cell Therapy in Preclinical Models Reona Sakemura, Claudia Manriquez Roman, Paulina Horvei, Ekene Ogbodo, Erin E. Tapper,Elizabeth L. Siegler, Carli M. Stewart, Kendall J. Schick, Ismail Can, Mohamad M. Adada, Evandro D. Bezerra, Lionel Aurelien A. Kankeu Fonkoua, Mehrdad Hefazi, Michael W. Ruff, Christian Augsberger, Jürgen Schanzer, Maria Patra-Kneuer, Christina Heitmüller, Stefan Steidl, Jan Endell, Wei Ding, Sameer A. Parikh, Neil E. Kay, Greg Nowakowski, Michelle J. Cox, Saad S. Kenderian Accepted as poster
(collaboration with Mayo Clinic)
#2412
Session Name: 622. Lymphomas: Translational-Non-Genetic: Poster II
Date: Sunday, December 12, 2021
Presentation Time: 6:00 PM – 8:00 PM
Location: Georgia World Congress Center, Hall B5
First-MIND First-MIND: Primary Analysis from a Phase Ib, Open-Label, Randomized Study to Assess Safety of Tafasitamab or Tafasitamab + Lenalidomide in Addition to R-CHOP in Patients with Newly Diagnosed Diffuse Large B-cell Lymphoma David Belada, Katerina Kopeckova, Juan Miguel Bergua Burgues, Don Stevens, Marc André, Ernesto Perez Persona, Petra Pichler, Philipp Staber, Marek Trneny, Bettina Brackertz, Neha Shah, Andrea Sporchia, John M. Burke, Grzegorz S. Nowakowski Accepted as poster
#3556
Session Name: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster III
Date: Monday, December 13, 2021
Presentation Time: 6:00 PM – 8:00 PM
Location: Georgia World Congress Center, Hall B5
First-MIND MRD Analysis Disease kinetics measured by ctDNA correlates with treatment response after tafasitamab in combination with R-CHOP with or without lenalidomide in first line treatment of DLBCL Mouhamad Khouja, Anke Schillhabel, Michaela Kotrova, Nikos Darzentas, Christian Kuffer, Derek Blair, Monika Brüggemann, Christiane Pott Accepted as poster with short presentation (collaboration with Univ. of Kiel) / #3498
Session Name: 621. Lymphomas: Translational-Molecular and Genetic: Poster III
Date: Monday, December 13, 2021
Presentation Time: 6:00 PM – 8:00 PM
Location: Georgia World Congress Center, Hall B5

About Tafasitamab
Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb(R) engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Monjuvi(R)(tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In January 2020, MorphoSys and Incyte entered into a collaboration and licensing agreement to further develop and commercialize tafasitamab globally. Monjuvi(R) is being co-commercialized by Incyte and MorphoSys in the United States. Incyte has exclusive commercialization rights outside the United States.

In Europe, Minjuvi(R) (tafasitamab) received conditional approval, in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials.

Minjuvi(R) and Monjuvi(R) are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name Monjuvi(R) in the U.S., and marketed by Incyte under the brand name Minjuvi(R) in the EU.

XmAb(R) is a registered trademark of Xencor, Inc.

About MANIFEST
MANIFEST is an open-label Phase 2 clinical trial of pelabresib (CPI-0610) in patients with myelofibrosis (MF), a rare cancer of the bone marrow that disrupts the body’s normal production of blood cells. Constellation is evaluating pelabresib in combination with ruxolitinib in JAK-inhibitor-naïve MF patients (Arm 3), with a primary endpoint of the proportion of patients with a >=35% spleen volume reduction from baseline (SVR35) after 24 weeks of treatment. Constellation Pharmaceuticals is also evaluating pelabresib either as a monotherapy in patients who are resistant to, intolerant of, or ineligible for ruxolitinib and no longer on the drug (Arm 1), or as add-on therapy in combination with ruxolitinib in patients with a sub-optimal response to ruxolitinib or MF progression (Arm 2). Patients in Arms 1 and 2 are being stratified based on transfusion dependent (TD) status. The primary endpoint for the patients in cohorts 1A and 2A, who were TD at baseline, is conversion to transfusion independence for 12 consecutive weeks. The primary endpoint for patients in cohorts 1B and 2B, who were not TD at baseline, is the proportion of patients with a >=35% spleen volume reduction from baseline after 24 weeks of treatment.

On November 4, 2021 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported a preclinical poster presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to be held December 11-14, 2021, in Atlanta, GA (Press release, ORIC Pharmaceuticals, NOV 4, 2021, View Source [SID1234594368]).

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Details of the poster presentation are as follows:

Title: CD73 inhibition overcomes immunosuppression and triggers autologous T-cell mediated multiple myeloma cell lysis in the bone marrow milieu
Abstract #: 2675
Date & Time: Sunday, December 12, 2021, 6:00 – 8:00 pm ET
Session: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational:
Poster II in Hall B5, Georgia World Congress Center
The presentation, in collaboration with Dr. Kenneth Anderson’s research laboratory at Dana-Farber Cancer Institute, will focus on the role of adenosine signaling in immunosuppression in patients with multiple myeloma and the ability of single agent CD73 inhibition to restore antitumor immune activity.

Key points of the abstract include:

In bone marrow aspirates from patients with relapsed or refractory multiple myeloma, an autologous ex vivo assay system comprising the multiple myeloma bone marrow milieu demonstrated that CD73-mediated adenosine activity suppressed the cytolytic activity of T-cells against tumor cells.
CD73 inhibition triggered activation of plasmacytoid dendritic cells and stimulated T-cell activation in ex vivo assays of multiple myeloma bone marrow microenvironment.
ORIC’s small molecule inhibitor of CD73 overcame immune suppression and triggered significant lysis and cell death of multiple myeloma cells by autologous T-cells in the bone marrow microenvironment.
Full abstracts are available for online viewing via the ASH (Free ASH Whitepaper) Annual Meeting website at www.hematology.org/meetings/annual-meeting. The Phase 1 trial of single agent ORIC-533 in patients with multiple myeloma is expected to initiate in 4Q 2021.

About ORIC-533

ORIC-533 is a highly potent, orally bioavailable small molecule inhibitor of CD73, a key node in the adenosine pathway believed to play a central role in resistance to chemotherapy and immunotherapy-based treatment regimens. ORIC-533 has demonstrated greater potency in preclinical studies compared to an antibody approach, as well as other small molecule inhibitors of CD73 and adenosine receptor antagonists. Preclinical data demonstrated that ORIC-533 binds CD73 with high affinity and effectively blocks adenosine-driven immunosuppression in a high AMP environment, reflective of AMP levels observed in tumors. In preclinical studies, nanomolar concentrations of ORIC-533 efficiently rescued cytotoxic T-cell function in the presence of high AMP concentrations, as well as in ex vivo bone marrow aspirates from relapsed or refractory multiple myeloma patients.

On November 4, 2021 IMV Inc. (NASDAQ: IMV; TSX: IMV), a clinical-stage company developing a portfolio of immune-educating cancer therapies, based on its novel DPX platform, to treat solid and blood cancers while preserving patients’ quality of life reported that it will hold a conference call and webcast on Thursday, November 11, 2021 at 8:00 a.m. ET to discuss the company’s third quarter 2021 financial and operational results (Press release, IMV, NOV 4, 2021, View Source [SID1234594367]).

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Financial analysts are invited to join the conference call by dialing (866) 211-3204 (U.S. and Canada) or (647) 689-6600 (international) and using the conference ID: 7079735 Other interested parties will be able to access the live audio webcast at this link: View Source The webcast will be recorded and will then be available on the IMV website for 30 days following the call.

On November 4, 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 three oral and five poster presentations for the Company’s induced pluripotent stem cell (iPSC) product platform were accepted for presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held from December 11-14, 2021 (Press release, Fate Therapeutics, NOV 4, 2021, View Source [SID1234594366]). The Company also plans to host a virtual investor event on Tuesday, December 14.

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The oral presentations will include updated Phase 1 clinical data of FT596, the Company’s universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master iPSC line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell antigen CD19; a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that augments NK cell activity. The Company previously reported interim Phase 1 clinical data of FT596 as monotherapy and in combination with rituximab for the treatment of relapsed / refractory B-cell lymphoma. As of the data cutoff date of June 25, 2021, in the second and third dose cohorts (90 million cells and 300 million cells, respectively) of the single-dose monotherapy and combination regimens, 10 of 14 patients (71%) achieved an objective response, including seven patients (50%) that achieved a complete response, on Day 29 as assessed by PET-CT scan per Lugano 2014 criteria. Treatment with FT596 was well tolerated, with two reported low-grade adverse events (one Grade 1, one Grade 2) of cytokine release syndrome (CRS) and no reported adverse events of immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GVHD).

The poster presentations will include updated Phase 1 clinical data of FT516, the Company’s universal, off-the-shelf NK cell cancer immunotherapy derived from a clonal master iPSC line engineered to express a novel hnCD16 Fc receptor. The Company previously reported interim Phase 1 clinical data of FT516 in combination with rituximab for the treatment of relapsed / refractory B-cell lymphoma. As of the data cutoff date of July 7, 2021, in the second and third multi-dose cohorts (90 million cells per dose and 300 million cells per dose, respectively), eight of 11 patients (73%) achieved an objective response, including six patients (55%) that achieved a complete response, on Day 29 of the second FT516 treatment cycle as assessed by PET-CT scan per Lugano 2014 criteria. Five of the 11 patients (45%) maintained their response without further therapeutic intervention, including four patients that remained in complete response (4.6-9.5 months) and one patient that remained in partial response (6.1 months). The multi-dose, multi-cycle treatment regimen was well tolerated, and no adverse events of CRS, ICANS, or GVHD were reported.

Additional presentations will include an oral presentation describing preclinical and clinical translational data of FT596; a poster presentation describing the making of the clonal engineered master iPSC line for FT819, which is created from a single iPSC that has a novel CD19-targeted 1XX CAR construct integrated into the T-cell receptor alpha constant (TRAC) locus; a poster presentation describing the preclinical activity of a novel multiplexed-engineered, dual CAR NK cell product candidate targeting B-cell maturation antigen (BCMA) and the alpha-3 domain of MICA/B in models of multiple myeloma; and a poster presentation describing the preclinical activity of multiplexed-engineered, iPSC-derived T cells incorporating three distinct tumor-targeting modalities (CAR, TCR and hnCD16).

Oral Presentations

Safety and Efficacy of FT596, a First-in-Class, Multi-Antigen Targeted, Off-the-Shelf, iPSC-Derived CD19 CAR NK Cell Therapy in Relapsed / Refractory B-Cell Lymphoma
Publication Number: 823
Session Name: 704. Cellular Immunotherapies: Expanding Targets and Cellular Sources for Immunotherapies
Presentation Date / Time: Monday, December 13, 2021; 4:30 PM
Room: Georgia World Congress Center, Georgia Ballroom 1-3
Off-the-Shelf, Multiplexed-Engineered iPSC-Derived NK Cells Mediate Potent Multi-Antigen Targeting of B-Cell Malignancies with Reduced Cytotoxicity Against Healthy B Cells
Publication Number: 407
Session Name: 703. Cellular Immunotherapies: Basic and Translational II
Presentation Date / Time: Sunday, December 12, 2021; 10:30 AM
Room: Georgia World Congress Center, B405-B407
Arming of iPSC-Derived NK Cells Expressing a Novel CD64 Fusion Receptor with Therapeutic Antibodies Represents a Novel Off-the-Shelf, Antigen-Targeting Strategy for Cancer
Publication Number: 406
Session Name: 703. Cellular Immunotherapies: Basic and Translational II
Presentation Date / Time: Sunday, December 12, 2021; 10:15 AM
Room: Georgia World Congress Center, B405-B407
Poster Presentations

Phase I Study of FT516, an Off-the-Shelf, iPSC-Derived NK Cell Therapy, in Combination with Rituximab in Patients with Relapsed / Refractory B-Cell Lymphoma
Publication Number: 3873
Session Name: 704. Cellular Immunotherapies: Clinical: Poster III
Presentation Date / Time: Monday, December 13, 2021; 6:00 PM
Room: Georgia World Congress Center, Hall B5
Clinical Manufacture of FT819: Use of a Clonal Multiplexed-Engineered Master Induced Pluripotent Stem Cell Line to Mass Produce Off-the-Shelf CAR T-Cell Therapy
Publication Number: 1766
Session Name: 711. Cell Collection and Processing: Poster I
Presentation Date / Time: Saturday, December 11, 2021; 5:30 PM
Room: Georgia World Congress Center, Hall B5
Combination of Three Unique Anti-Tumor Modalities Engineered into iPSC-Derived T Cells Demonstrate a Synergistic Effect in Overcoming Tumor Heterogeneity and Cancer Escape
Publication Number: 2793
Session Name: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Presentation Date / Time: Sunday, December 12, 2021; 6:00 PM
Room: Georgia World Congress Center, Hall B5
Dual Chimeric Antigen Receptor Approach Combining Novel Tumor Targeting Strategies Circumvents Antigen Escape in Multiple Myeloma
Publication Number: 1718
Session Name: 703. Cellular Immunotherapies: Basic and Translational: Poster I
Presentation Date / Time: Saturday, December 11, 2021; 5:30 PM
Room: Georgia World Congress Center, Hall B5
Off-the-Shelf, iPSC-Derived CAR NK Cells Multiplexed-Engineered for the Avoidance of Allogeneic Host Immune Cell Rejection
Publication Number: 2795
Session Name: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Presentation Date / Time: Sunday, December 12, 2021; 6:00 PM
Room: Georgia World Congress Center, Hall B5
The accepted abstracts are available online through the ASH (Free ASH Whitepaper) conference website (www.hematology.org/Annual-Meeting/Abstracts/).

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.

About FT516
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in a multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumors resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

About FT596
FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that augments NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors enhances cytotoxic activity, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell lymphoma as a monotherapy and in combination with rituximab, and for the treatment of relapsed / refractory chronic lymphocytic leukemia (CLL) as a monotherapy and in combination with obinutuzumab (NCT04245722).

About FT819
FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease. FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia (Valamehr et al. 2020). FT819 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

On November 4, 2021 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage biotechnology company using its ARCUS genome editing platform to develop allogeneic CAR T and in vivo gene editing therapies, reported that investigators involved with the Phase 1/2a study of PBCAR0191 in Relapsed/Refractory (R/R) non-Hodgkin’s lymphoma (NHL) and B-cell acute lymphoblastic leukemia (B-ALL), will present new data during two oral presentations at the 63rd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) taking place December 11-14, 2021 (Press release, Precision Biosciences, NOV 4, 2021, View Source [SID1234594365]).

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"We are encouraged by the response rates seen in this heavily pre-treated patient population, and that a treatment strategy with enhanced lymphodepletion mitigated PBCAR0191 rejection and improved peak CAR T cell expansion and persistence, compared to standard lymphodepletion, with predictable toxicity," said Alan List, MD, Chief Medical Officer of Precision BioSciences. "We look forward to sharing additional patient outcome, durability, and safety data for PBCAR0191 at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting."

The abstracts accepted by the ASH (Free ASH Whitepaper) are now available at www.hematology.org, and will be presented during the following oral presentation sessions:

Session Name: 626, Abstract #302. Aggressive Lymphomas Prospective Therapeutic Trials: Challenging Populations
Oral Presentation Title: Allogeneic CAR-T PBCAR0191 with Intensified Lymphodepletion is Highly Active in Subjects with Relapsed/Refractory B-cell Malignancies
Presenting Author: Bijal Shah, M.D., Moffitt Cancer Center
Date/Time: Saturday, December 11, 2021 at 4:15 PM ET
Location: Georgia World Congress Center, B401-B402

Session Name: 704, Abstract #650 Cellular Immunotherapies: Allogeneic CARs and CARs for T Cell Lymphomas
Oral Presentation Title: Preliminary Safety and Efficacy of PBCAR0191, an Allogeneic ‘Off-the-Shelf’ CD19-Directed CAR-T for Patients with Relapsed/Refractory (R/R) CD19+ B-ALL
Presenting Author: Nitin Jain, M.D., The University of Texas MD Anderson Cancer Center
Date/Time: Monday, December 13, 2021 at 10:45 AM ET
Location: Georgia World Congress Center, Sidney Marcus Auditorium

Published abstracts report on key interim clinical evaluations of CD19+ NHL or B-ALL subjects treated with PBCAR0191.

Abstract #302: For 21 subjects with Relapsed/Refractory (R/R) B-cell malignancies (16 NHL, 5 B-ALL) who received PBCAR0191 following enhanced lymphodepletion1 as of July 1, 2021:

PBCAR0191 demonstrated a safety profile with no Grade 3 CRS, one Grade 3 self-limited ICANS, no evidence of GvHD, and one infectious death at Day 54, deemed possibly related to treatment.
83% (15/18) of evaluable subjects experienced a complete response (CR) rate or complete remission with incomplete marrow recovery (CRi); 62% (8/13) of NHL subjects and 80% (4/5) of B-ALL subjects, respectively.
20% (3/15) of responders demonstrated durability of response greater than 6 months, with 3 additional responders not yet having reached a 6-month evaluation threshold.
Compared to standard lymphodepletion2, enhanced lymphodepletion mitigated PBCAR0191 rejection to markedly improve peak CAR T cell expansion and persistence with area under the curve increasing 80-fold.
Among 6 subjects who progressed following prior CD19 CAR therapy (5 NHL, 1 B-ALL), the overall response rate was 83% (5/6) with 67% (4/6) achieving a CR, including an ongoing MRD negative CR in a B-ALL subject of >6 months.
Abstract #650: For 15 subjects with R/R B-cell acute lymphoblastic leukemia including 11 subjects who received PBCAR0191 Dose Level 3/4a3 and 4 subjects who received PBCAR0191 Dose Level 4b4 as of August 2, 2021:

PBCAR0191 demonstrated a safety profile with no cases of GvHD, no Grade ≥3 CRS, and one case of Grade 3 ICANS, which resolved within 48 hours.
For subjects who received either Dose Level 3/4a following enhanced lymphodepletion or Dose Level 4b following standard lymphodepletion, 78% (7/9) achieved a high CR or CRi rate; 56% (5/9) maintained the CR at day 28 or later potentially securing an adequate window to bridge to allogeneic stem cell transplant.
Use of enhanced lymphodepletion or higher doses of PBCAR0191 resulted in substantial improvements in peak CAR T cell expansion and area under the curve.