On June 22, 2020 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of checkpoint antibodies, cell therapy, adjuvants, and vaccines designed to activate immune response to cancers and infections, reported that it will make a scientific presentation today on optimal anti-cancer combinations with Fc enhanced anti-CTLA-4, AGEN1181, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting (Press release, Agenus, JUN 22, 2020, View Source [SID1234561292]).

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"AGEN1181 is an Fc-engineered anti-CTLA-4 that has shown exciting clinical activity in an early phase 1 clinical trial, which was recently presented at ASCO (Free ASCO Whitepaper)," said Dr. Antoine Tanne, Lead Scientist, Agenus Immune Biology Team. "Today, at AACR (Free AACR Whitepaper), we report that combinations with AGEN1181 demonstrate curative responses in preclinical models resistant to anti-PD-1. These data illustrate the potential of combining allogeneic cell therapies with checkpoint antibodies, such as AGEN1181, to deliver curative benefit in difficult to treat settings."

Title: "Expanding the therapeutic potential of anti-PD-1 and anti-CTLA-4 therapy with innovative Fc engineering and rationale combinations for the treatment of solid tumors"
Presenter: Antoine J. Tanne. Ph.D
Abstract: 922 / 24
Session: Combination Immunotherapies 1
Date/Time: June 22, 2020, 9am-6pm

Presentations will be available for on-demand viewing online at View Source!/9045/sessions/@sessiontype=Virtual%20Symposium/1

On June 22, 2020 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, taking place June 22-24, 2020 (Press release, MacroGenics, JUN 22, 2020, View Source [SID1234561287]).

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"We are pleased to present data at this year’s AACR (Free AACR Whitepaper) that highlight three platform technologies upon which multiple molecules are being developed at MacroGenics. We are presenting preclinical data for MGC018, our investigational antibody-drug conjugate targeting B7-H3, that provide evidence for an immune-mediated anti-tumor mechanism, as well as a rationale for clinical investigation of this molecule in combination with checkpoint blockade. Separately, we are presenting data from our novel Fc-engineered, bispecific DART molecule that binds CD25 and CTLA-4 that is capable of depleting tumor-infiltrating regulatory T cells with high specificity in vitro," said Ezio Bonvini, M.D., Senior Vice President and Chief Scientific Officer of MacroGenics. "Finally, one of the clinical investigators for flotetuzumab, our investigational CD123 x CD3 DART molecule, will be presenting preclinical data from his research with this molecule during an oral Education Session."

AACR II Presentations

MGC018, a duocarmycin-based antibody-drug conjugate targeting B7-H3, exhibits immunomodulatory activity and enhanced antitumor activity in combination with checkpoint inhibitors

Poster Session: PO.ET07.01 – Cell Surface Antigens and Receptors as Drug Targets

MGC018 is an investigational antibody-drug conjugate targeting B7-H3 that has shown preliminary anti-tumor activity in an ongoing Phase 1 dose escalation study in patients with advanced solid tumors. The poster presented at AACR (Free AACR Whitepaper) describes preclinical data suggesting that MGC018 can promote immune surveillance or stimulate immune responses to dying cancer cells that led to immunological memory, and when combined with checkpoint blockade may enhance anti-tumor activity.

These studies used a mouse model system designed to evaluate anti-tumor activity in an intact and functioning immune system. In this in vivo model, MGC018 demonstrated targeted activity against tumors expressing human B7-H3. Mechanistically, in vitro data suggested that MGC018 induced immunogenic cell death of target cells with the translocation of calreticulin to the cell surface during apoptosis. In addition, treatment with MGC018 in this model system led to an increased infiltration of T cells into the tumor microenvironment. Depleting these T cells attenuated the anti-tumor activity by MGC018, demonstrating their role in mediating response. Furthermore, MGC018 combined with an anti-PD-1 antibody enhanced anti-tumor activity observed in this study. Finally, mice that had achieved a complete response to initial treatment with MGC018 with or without checkpoint blockade survived longer when re-challenged with tumor without subsequent treatment compared to mice that had not received treatment with MGC018, suggesting immunological memory.

Investigational CD25 x CTLA-4 bispecific DART molecule for depletion of tumor infiltrating Tregs via an enhanced Fc-dependent effector mechanism

Poster Session: PO.IM02.23 – Therapeutic Antibodies 1

The poster presented at AACR (Free AACR Whitepaper) described a preclinical bispecific CD25 x CTLA-4 DART molecule containing an Fc region engineered to enhance clearance of target cells by antibody-dependent cellular cytotoxicity. This molecule was designed to deplete tumor-associated regulatory T cells co-expressing CD25 and CTLA-4 to reduce immune suppression mediated by these cells but preserve effector T cell function. CD25 is the alpha subunit of IL-2 receptor and CTLA-4 is a molecule involved in regulatory T cell function.

In vitro studies showed that the Fc-engineered bispecific CD25 x CTLA-4 DART molecule depleted regulatory T cells, with minimal effect on effector T cells. This depletion of regulatory T cells was shown to occur through an Fc-dependent mechanism, as a control CD25 x CTLA-4 DART molecule with an inactivated Fc domain had no effect in this assay. In addition, the bispecific CD25 x CTLA-4 DART molecule preserved cytotoxic T cell effector function in vitro compared to a combination of Fc-engineered monoclonal antibodies independently targeting CD25 and CTLA-4.

Immune escape after bone marrow transplantation: Hiding in plain sight

Educational Session: ED52 – Immunotherapy, Immune Evasion in Myeloid Malignancies, and Therapeutic Implications

John F. DiPersio, M.D., Ph.D., from Washington University School of Medicine in St. Louis, will present an overview of his research related to immune evasion and mechanisms of relapse after allogeneic hematopoietic cell transplantation (allo-HCT). The presentation will include preclinical data on flotetuzumab (MGD006), an investigational CD123 x CD3 bispecific DART molecule, suggesting a potential role for this molecule in treating patients with acute myeloid leukemia whose disease is relapsing after allo-HCT.

Date: June 24, 2020
Time: 5:30 – 5:50pm ET
Location: AACR (Free AACR Whitepaper) Virtual Annual Meeting II at www.aacr.org

The posters will be available on the Events & Presentations page on MacroGenics’ website at View Source

On June 22, 2020 CytomX Therapeutics, Inc. (Nasdaq: CTMX) reported that its partner Bristol Myers Squibb presented preclinical data from BMS-986249 and BMS-986288, anti-CTLA-4 Probody therapeutics generated with CytomX’s novel Probody technology platform (Press release, CytomX Therapeutics, JUN 22, 2020, View Source [SID1234561285]). The electronic poster #4551 titled "Preclinical characterization of novel anti-CTLA-4 prodrug antibodies with an enhanced therapeutic index" was presented as part of the Therapeutic Antibodies 3 Session at the American Association of Cancer Research’s (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting II.

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BMS-986249 is a Probody version of the anti-CTLA-4 antibody ipilimumab (Yervoy). In February 2020, Bristol Myers Squibb treated the first patient in a Part 2a randomized cohort expansion in an ongoing Phase 1/2a trial of BMS-986249 in combination with Opdivo (nivolumab) in patients with metastatic melanoma. Additional information is available at ClinicalTrials.gov using the Identifier NCT03369223.

BMS-986288 is a Probody of a nonfucosylated version of ipilimumab (anti-CTLA-4 NF). In September 2019, Bristol Myers Squibb initiated the dose escalation phase of a Phase 1/2a clinical trial of BMS-986288 administered as monotherapy and in combination with nivolumab in patients with selected advanced solid tumors. Additional information is available at ClinicalTrials.gov using the Identifier NCT03994601.

These Probody programs, designed to optimize the therapeutic index of CTLA-4-directed therapy, arose from the companies’ 2014 worldwide oncology license and collaboration agreement.

"This important work within our Bristol Myers Squibb alliance is aimed at broadening the utility of this foundational immunotherapeutic approach to the treatment of cancer," said Sean McCarthy D.Phil., president, chief executive officer and chairman of CytomX Therapeutics. "We look forward to seeing the full potential of these programs as they continue to advance in the clinic."

On June 22, 2020 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported the presentation of new preclinical data from its JTX-1811 program and translational data from its ongoing vopratelimab program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting (Press release, Jounce Therapeutics, JUN 22, 2020, View Source [SID1234561284]).

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"The progress we have made to date with both JTX-1811, our anti-CCR8 antibody, and vopratelimab, our ICOS agonist, represent the strength of our Translational Science Platform as we continue to gain new insights about the tumor microenvironment from preclinical studies through clinical development. We are excited to share the first results from our anti-CCR8 program, demonstrating JTX-1811’s ability to deplete immunosuppressive tumor infiltrating T regs and to provide synergistic activity with PD-1 inhibitors in otherwise PD-1 inhibitor resistant tumor models," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "Additionally, analyses of the vopratelimab-associated ICOS hi CD4 T cells from long-term responders in the ICONIC trial provide more insight into the potential contribution of these cells to durable clinical benefit. Both presentations represent our commitment to translational science and deep understanding of the tumor immune microenvironment as we strive to provide meaningful clinical benefit to patients with cancer."

Key highlights from the poster titled, "Preclinical evaluation of JTX-1811, an anti-CCR8 antibody with enhanced ADCC activity, for preferential depletion of tumor-infiltrating regulatory T cells" include:

Tumor-infiltrating T-regulatory (TITR) cells suppress anti-tumor immunity in the tumor microenvironment.
CCR8 may be a superior target for TITR cells because it is expressed at high densities on the cell surface of tumor T-regulatory cells.
A surrogate antibody specific for mouse CCR8 showed single agent and synergistic combination activity with PD-1 inhibitors in anti-PD-1 resistant murine tumor models.
An antibody with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) may optimize the window for depletion of human TITR cells.
Based on these preclinical data, JTX-1811, a high affinity CCR8-specific humanized monoclonal antibody with enhanced ADCC activity, is being developed for the selective depletion of TITR cells.
Key highlights from the poster titled, "ICOS hi CD4 T cells emerging on vopratelimab treatment have Th1, central memory, and Tfh characteristics that may contribute to durability of clinical responses" include:

The emergence of a peripheral blood ICOS hi CD4 T cell population is associated with durable responses to vopratelimab alone and in combination with nivolumab.
The ICOS hi phenotype is induced in an antigen-specific manner through stimulation of the T cell receptor, and vopratelimab is only active on primed ICOS hi CD4 T cells.
The ICOS hi CD4 T cell population within peripheral blood of ICONIC responders is comprised of Th1, T central memory (Tcm) and T follicular helper (Tfh) subsets, which may be critical for direct anti-tumor effects as well as durability of clinical responses.
Retrospective flow analysis of publicly available mass cytometry data demonstrated ipilimumab or ipilimumab in combination with nivolumab induced enrichment of a robust Th1 but not Tcm or Tfh phenotypes within peripheral blood.
In a hCTLA-4 knock-in mouse model, preliminary assessment of anti-tumor efficacy demonstrated added activity when scheduled dosing of an ICOS agonist included administration following ICOS hi induction by ipilimumab.
In the ongoing EMERGE study, Jounce is testing the hypothesis that the addition of an ICOS agonist following ipilimumab-induction of ICOS hi CD4 T cells may enhance clinical benefit.
Both posters and audio presentations are available under "Publications" in the "Our Pipeline" section of the Jounce Therapeutics website at www.jouncetx.com.

About JTX-1811
JTX-1811 is a monoclonal antibody designed to selectively deplete immunosuppressive tumor-infiltrating T regulatory (TITR) cells. The target of JTX-1811 is CCR8, a chemokine receptor enriched on TITR cells. When JTX-1811 binds to CCR8, it targets TITR cells for depletion by enhanced antibody-dependent cellular cytotoxicity mechanism. Jounce expects to file an Investigational New Drug (IND) application in the first half of 2021.

About Vopratelimab
Jounce’s lead product candidate, vopratelimab, is a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO Stimulator, a protein on the surface of certain T cells found in many solid tumors. Vopratelimab was previously assessed in the Phase 1/2 ICONIC trial and was found to have an acceptable safety profile and be well-tolerated, alone and in combination with each of the anti-PD-1 antibodies nivolumab and pembrolizumab, and ipilimumab, an antibody that binds to CTLA-4. Vopratelimab is currently being assessed in the Phase 2 EMERGE clinical trial in a sequenced combination with ipilimumab in patients with non-small cell lung cancer (NSCLC) who have progressed on or after both a platinum-based regimen and a PD-1 or PD-L1 inhibitor. Jounce is also planning to initiate the Phase 2 SELECT clinical trial of vopratelimab with its investigational PD-1 inhibitor, JTX-4014, in TISvopra biomarker-selected patients who are PD-1 inhibitor naïve in second line NSCLC.

On June 22, 2020 Spectrum Pharmaceuticals, Inc. (NASDAQ-GS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported preclinical data evaluating the administration of ROLONTIS (eflapegrastim) on the same day as chemotherapy (Press release, Spectrum Pharmaceuticals, JUN 22, 2020, View Source [SID1234561283]). The duration of neutropenia in a rat model of chemotherapy induced neutropenia (CIN) was observed to be significantly shorter with eflapegrastim versus pegfilgrastim, regardless of the timing of administration: concomitantly or on the same day post-chemotherapy at 2, 5 or 24 hours post-chemotherapy.

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The poster titled "Chemotherapy induced neutropenia in rats following administration of eflapegrastim or pegfilgrastim on the same day at three different time points and at 24 hours post-chemotherapy" was part of today’s Special Populations, Survivorship, Outcomes, and Supportive Care session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II. ROLONTIS is an investigational drug not approved by the U.S. Food and Drug Administration (FDA) and the BLA (Biologics License Application) is currently under active review by the agency for the treatment of chemotherapy induced neutropenia with a PDUFA date of October 24, 2020.

"These data in rats suggest that eflapegrastim administered at the time of chemotherapy, rather than waiting 24 hours, may be able to provide prophylaxis against chemotherapy induced neutropenia," said Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. "Based on these preclinical results, we recently initiated a Phase 1 clinical trial to compare the effect of same day dosing of eflapegrastim on the duration of neutropenia in patients with early-stage breast cancer when administered on the same day, at varying intervals following docetaxel and cyclophosphamide chemotherapy."