On April 10, 2021 ITM AG reported the presentation of a trial-in-progress poster highlighting its ongoing Phase III trial COMPETE with n.c.a. 177Lu-Edotreotide in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) at the virtual American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 (Press release, ITM Isotopen Technologien Munchen, APR 10, 2021, View Source [SID1234577857]). The poster will be presented in video format as part of the Phase III trials in progress poster session by Mona M. Wahba, MD, Deputy Chief Medical Officer at ITM. It will be available following the e-poster website launch on April 10, 2021, at 8:30 am ET / 2:30 pm CET and remain available for viewing through June 21, 2021.

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"GEP-NETs are often diagnosed at an advanced stage in patients who have a high unmet medical need. N.c.a. 177Lu-Edotreotide has already shown very promising signs of efficacy and safety in this patient population in a Phase II study and we look forward to building on these results in COMPETE, with the goal of improving the treatment options that are available for these patients," stated Philip E. Harris, PhD, Chief Medical Officer at ITM. "The AACR (Free AACR Whitepaper) Annual Meeting is one of the key oncology conferences in our industry and we welcome the opportunity to present our lead program as well as to discuss the potential benefits of targeted radiopharmaceuticals such as n.c.a. 177Lu-Edotreotide with the global scientific community."

The presented COMPETE trial (NCT03049189) is a prospective, randomized, controlled, open-label, multi-center Phase III study to evaluate the efficacy and safety of n.c.a. 177Lu-Edotreotide PRRT compared to mTOR inhibitor everolimus in patients with inoperable, progressive, somatostatin receptor-positive (SSTR+) GEP-NETs. The study is currently recruiting patients in 14 countries. As part of the study, 300 patients with progressive SSTR+ Grade 1 and 2 GEP-NETs are being randomized, of which 200 receive up to 4 cycles of n.c.a. 177Lu-Edotreotide (7.5 GBq/cycle) every 3 months or until diagnosis of progression, while 100 patients receive 10 mg everolimus daily for 24 months, or until diagnosis of progression. The overall study duration per patient will be 30 months. Primary objective of the study is to demonstrate prolonged progression free survival (PFS) in patients in the n.c.a. 177Lu-Edotreotide arm vs. everolimus, while secondary objectives include safety, objective response rates and overall survival after 5 years follow-up.

The initiation of the Phase III study was based on the successful completion of a Phase II study that evaluated the efficacy and safety of n.c.a. 177Lu-Edotreotide (177Lu-DOTATOC) in 56 patients with metastasized and progressive NETs (50% gastroenteral, 26.8% pancreatic, 23.2% other primary sites). The results demonstrated the promising efficacy and safety that ITM’s lead candidate can provide in this advanced patient population, achieving a median PFS (mPFS) of 17.4 months and an overall survival of 34.2 months, respectively, with a mPFS of 34.5 months for GEP-NETs. Objective response rates (Complete/Partial Responses) were 54.2% in GEP-NETs, with complete response rates of 25%, of which 78% were maintained throughout the follow-up period. In addition, no serious adverse events were observed. These results indicate that n.c.a. 177Lu-Edotreotide has a major potential to induce objective tumor responses and sustained disease control in progressive neuroendocrine tumors. The observed safety profile suggests a particularly favorable therapeutic index, including in patients with impaired bone marrow or renal function, reflecting the low uptake of n.c.a. 177Lu-Edotreotide by normal organs. The ongoing Phase III COMPETE study will now aim to confirm and further build on these results.

Presentation information
Title: COMPETE Phase III Trial – Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-Edotreotide vs. Everolimus in Progressive GEP-NET
Abstract No: 5201
Session: Phase III Clinical Trials in Progress
Presenter: Mona M. Wahba, MD

Mona M. Wahba is available for questions and discussions via the chat box function of the AACR (Free AACR Whitepaper) poster section and will respond within 24 hours. Meetings can also be requested using the AACR (Free AACR Whitepaper) system.

The poster will also be made available on the company’s website under the event section.

On April 10, 2021 ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that a poster highlighting preclinical data for its novel ADAM9-targeting ADC, IMGC936, which is being investigated in multiple solid tumor types, is being presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting April 10-15, 2021 (Press release, ImmunoGen, APR 10, 2021, View Source [SID1234577856]).

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"ADAM9 is overexpressed in a wide range of solid tumors and minimally expressed on normal tissue, which makes it an ideal ADC target," said Eric Westin, MD, Vice President, Clinical Development and Translational Sciences at ImmunoGen. "IMGC936 showed compelling anti-tumor activity against multiple patient-derived xenograft models with clinically relevant levels of ADAM9 and was well-tolerated across all models tested. We continue to enroll patients in our Phase 1 dose-escalation study of IMGC936 in multiple tumor types and look forward to sharing initial data by the end of 2021 or early 2022."

POSTER PRESENTATION

Title: "IMGC936, an investigational ADAM9-targeting antibody-drug conjugate, is active against patient-derived ADAM9-expressing xenograft models"
Day/Time: Saturday, April 10, 2021 at 8:30 AM ET
Session Category: Immunology
Session Title: PO.IM02.10 – Therapeutic Antibodies, Including Engineered Antibodies
Abstract: 1841
Additional information can be found at www.aacr.org.

ABOUT IMGC936
IMGC936 is a first-in-class ADAM9-targeting antibody-drug conjugate (ADC) that is comprised of a humanized antibody engineered to include a YTE mutation for enhanced exposure through improved recycling, a tri-peptide cleavable linker stable in circulation, and a next-generation DM21 maytansinoid payload, which is more potent and hydrophobic, resulting in increased bystander activity.

ADAM9 is a cell surface protein that belongs to the ADAM (a disintegrin and metalloproteinase) family of proteases, which have been implicated in cytokine and growth factor shedding and cell migration. Dysregulation of ADAM9 has been involved in tumor progression and metastasis, as well as pathological neovascularization. ADAM9 is overexpressed in multiple solid tumor types (e.g., non-small cell lung, gastric, pancreatic, triple-negative breast, and colorectal cancers) and minimally expressed on normal tissue, making ADAM9 an attractive target for ADC development.

IMGC936 is being co-developed with MacroGenics and is currently in a Phase 1 study enrolling patients with solid tumors that express ADAM9.

On April 10, 2021 Scholar Rock (NASDAQ:SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, being held virtually from April 10-15 (Press release, Scholar Rock, APR 10, 2021, View Source [SID1234577855]).

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The e-poster will provide an overview of the development of biomarker assays that are being implemented to support the DRAGON Phase 1 proof-of-concept trial (NCT04291079). The DRAGON trial is evaluating SRK-181, a selective inhibitor of latent TGFβ1, in patients with locally advanced or metastatic solid tumors that have shown primary resistance to checkpoint inhibitor therapies.

Details of the poster presentation at the meeting are as follows:

Title: "Development of a Comprehensive Biomarker Strategy to Support the Latent TGFβ1 Inhibitor SRK-181 Phase 1 Clinical Trial, DRAGON" (P.1801)
Available for on-demand viewing starting April 10, 2021 at 8:30am ET during the Modifiers of the Tumor Microenvironment Session.
About SRK-181
SRK-181 is a selective inhibitor of TGFβ1 activation and is an investigational product candidate being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies. TGFβ1 is the predominant TGFβ isoform expressed in many human tumor types. Based on analyses of various human tumors that are resistant to anti-PD-(L)1 therapy, data suggest TGFβ1 is a key contributor to the immunosuppressive microenvironment, excluding and preventing entry of cytotoxic T cells into the tumor, thereby inhibiting anti-tumor immunity (1). Scholar Rock believes SRK-181, which specifically targets the latent TGFβ1 isoform, has the potential to overcome this immune cell exclusion and induce tumor regression when administered in combination with anti-PD-(L)1 therapy while potentially avoiding toxicities associated with non-selective TGFβ inhibition. The DRAGON Phase 1 proof-of-concept clinical trial (NCT04291079) in patients with locally advanced or metastatic solid tumors is ongoing. The efficacy and safety of SRK-181 have not been established. SRK-181 has not been approved for any use by the FDA nor any other regulatory agency.

(1) Martin et al., Sci. Transl. Med. 12: 25 March 2020

On April 10, 2021 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting myeloid checkpoints, reported the first public presentation of preclinical data for its first-in-class myeloid checkpoint inhibitor, IO-202, an LILRB4 antagonist antibody, in solid tumors (Press release, Immune-Onc Therapeutics, APR 10, 2021, View Source [SID1234577854]). The electronic poster will be presented as part of the Immune Checkpoints Session of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 (#AACR21), taking place virtually April 10-15, 2021.

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Myeloid cells are abundant and often immune suppressive in the solid tumor microenvironment (TME). LILRB4 (also known as ILT3) is expressed on monocytic myeloid cells, offering rationale for investigating the potential of IO-202 in solid tumors. IO-202 may be combined with anti-PD-(L)1, other immunotherapies, and/or immunogenic chemotherapy in future investigations of novel treatment approaches for solid tumors.

"It is widely recognized that only a minority of patients achieve a complete or durable response to T cell checkpoint inhibitor therapies. IO-202 is a first-in-class myeloid checkpoint inhibitor targeting LILRB4, a protein that contributes to cancer immune evasion, not only in blood cancers but also in many solid tumor types," said An Song, Ph.D., chief scientific officer of Immune-Onc. "Today, for the first time, we report preclinical data showing that IO-202 enhances dendritic cell function and T cell activation in vitro and inhibits tumor growth in a solid tumor model in vivo. As we move toward the clinic, these data improve our understanding of the role of LILRB4 in the tumor microenvironment and reinforce the therapeutic potential of IO-202 in solid tumors."

AACR E-Poster Presentation Details:

Title: IO-202, a first-in-class LILRB4 antagonist antibody, activates dendritic cells and inhibits solid tumor growth in preclinical studies (View Source!/9325/presentation/2730)

Session PO.IM02.03 – Immune Checkpoints

Abstract Number: 1629

ABOUT LILRB4 (also known as ILT3)

LILRB4, also known as ILT3, is an immune inhibitory transmembrane protein found on monocytic myeloid cells, including antigen presenting cells (APCs). LILRB4 inhibits APC activation, resulting in immune tolerance. LILRB4 is also expressed on certain hematologic cancer cells and monocytic myeloid cells in the solid tumor microenvironment. Immune-Onc and The University of Texas published pioneering research in Nature illuminating the role of LILRB4 in immune suppression and tumor infiltration in acute myeloid leukemia (AML).

About IO-202

Immune-Onc’s lead asset, IO-202, is a first-in-class LILRB4 antagonist antibody with broad potential as an immunotherapy in both blood cancers and solid tumors. In hematologic malignancies, preclinical studies showed that IO-202 converts a "don’t kill me" to a "kill me" signal by activating T cell killing and converts a "don’t find me" to a "find me" signal by inhibiting infiltration of blood cancer cells.

In September 2020, Immune-Onc initiated a Phase I trial evaluating IO-202 in AML with monocytic differentiation and in chronic myelomonocytic leukemia (CMML). The U.S. Food and Drug Administration granted IO-202 Orphan Drug Designation for treatment of AML in October 2020.

On April 10, 2021 Tallac Therapeutics, Inc., a privately held biopharmaceutical company harnessing the power of innate and adaptive immunity to fight cancer, reported the first presentation of preclinical data demonstrating potent single-agent anti-tumor activity in preclinical cancer models with systemically administered TAC-001, the company’s lead clinical candidate from its novel Toll-like Receptor Agonist Antibody Conjugate (TRAAC) platform (Press release, Tallac Therapeutics, APR 10, 2021, View Source [SID1234577853]). The data will be presented today as part of the Immunomodulatory Agents and Interventions Session at Week I of the American Association of Cancer Research’s (AACR) (Free AACR Whitepaper) 2021 Virtual Annual Meeting (#AACR21) taking place April 10-15, 2021.

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Toll-like receptor (TLR) agonists are a novel class of immunotherapy that generate both an innate and adaptive immune response which may produce more robust and durable anti-cancer immunity to help overcome resistance to standard-of-care oncology treatments. TLR9 is a key intracellular TLR present in broad immune cell populations such as B lymphocytes and myeloid cells. Recent studies have shown that the likelihood of patients responding to immune checkpoint inhibitor therapy may depend on B cells in the tumor.i B cells play pivotal roles in the immune defense system, which bridge the innate and the adaptive immunities against cancers.ii In preclinical studies, the activation of TLR9 in human and mouse models drives B cell proliferation and differentiation.iii

"The results presented today at AACR (Free AACR Whitepaper) elucidate the unique properties of TAC-001 responsible for integrating B cells and TLR9 activation which trigger innate and adaptive immune responses to create potent, systemically delivered anti-tumor immunity across solid tumor types," said Dr. Hong I. Wan, president, CEO and co-founder of Tallac Therapeutics. "The emerging data on TAC-001 continues to strengthen our understanding of the roles that B cells and TLR9 activation play in eliciting anti-tumor immunity in checkpoint inhibitor resistant and refractory settings and will help guide our clinical development strategy."

In the e-poster, titled "TAC-001, a toll-like receptor 9 (TLR9) agonist antibody conjugate targeting B cells, promotes anti-tumor immunity and favorable safety profile following systemic administration in preclinical models," investigators present data providing evidence that in vitro targeted delivery of TAC-001 leads to superior TLR9 activation in B cells, increased expression of co-stimulatory molecules and cross-presentation leading to T cell proliferation. In vivo, TAC-001 demonstrated robust, curative and durable single agent anti-tumor activity in checkpoint inhibitor resistant and refractory tumor models. Additionally, the systemic administration of TAC-001 was shown to trigger both innate and adaptive immunity by increasing B cell infiltration, T effector cell functions and modulation in suppressive myeloid cells within the tumor microenvironment. These results support the development of TAC-001 for a broad range of solid tumor malignancies.

AACR Poster Presentation Details:

Title: TAC-001, a toll-like receptor 9 (TLR9) agonist antibody conjugate targeting B cells, promotes anti-tumor immunity and favorable safety profile following systemic administration in preclinical models
Session Type: E-Poster Session
Session Category: Immunology
Session Title: Immunomodulatory Agents and Interventions
Track: Immunology, Clinical Research Excluding Trials
Permanent Abstract Number: 1721
About TAC-001

TAC-001 is a Toll-like Receptor Agonist Antibody Conjugate (TRAAC) comprised of a potent Toll-like Receptor 9 agonist (T-CpG) conjugated to an anti-CD22 antibody, a receptor restricted to B cells. TAC-001 is designed to systemically deliver T-CpG to B cells by binding to CD22, leading to internalization of TAC-001, TLR9 signaling, B cell activation and a cascade of immune reactions. Preclinical studies demonstrate that the innate and adaptive immune responses triggered by TAC-001 leads to potent anti-tumor activity. TAC-001 is being developed to systemically deliver targeted immune activation in solid tumor cancers.