On April 10, 2021 Tachyon Therapeutics, Inc. ("Tachyon" or "the Company"), a research and development biotechnology company, reported a presentation of data of the Company’s novel compound, TACH101, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting (Press release, Tachyon Therapeutics, APR 10, 2021, View Source [SID1234577858]). TACH101, Tachyon’s lead product candidate, is a first-in-class, highly-selective inhibitor of KDM4 histone demethylase . AACR (Free AACR Whitepaper) is being held virtually from April 10-15 and May 17-21, 2021.

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"We are excited to be presenting for the first time data on TACH101, a novel first-in-class inhibitor of KDM4," stated Frank Perabo, MD, PhD, CEO of Tachyon Therapeutics. "KDM4 is an important epigenetic regulator of processes responsible for genomic instability, replicative immortality, evasion of apoptosis, deficiency in DNA repair and ability to metastasize across multiple tumor types. Extensive preclinical work shows compelling data for TACH101 to have broad potential in cancer treatment. To date, no small molecule inhibitor of KDM4 has reached clinical stage development, thus Tachyon would be the first to investigate this mechanistic pathway in a clinical trial."

Highlights from the AACR (Free AACR Whitepaper) presentation are summarized below:

TACH101 was broadly effective in the majority of 300 cancer cell lines screened.
TACH101 treatment induced cell cycle arrest in a dose-dependent manner, increasing the proportion of cells in S-phase by up to 3.2-fold after 72 hours of treatment.
TACH101 was potent in inducing apoptosis in human colorectal, esophageal, and triple negative breast cancer cell lines; the half maximal effective concentrations (EC50s) were in the nanomolar levels (ranging from 33 – 92 nM).
In vivo, TACH101 demonstrated effective tumor control in xenograft models including colorectal, esophageal, gastric, breast, and lymphoma with tumor growth inhibition of up to 100%.
TACH101-treated tumors showed a significant reduction in the population of cancer stem cells by 4.4-fold.
Pharmacokinetic studies showed TACH101 exhibited low clearance, moderate volume of distribution, and good oral bioavailability in mouse, rat, and dog, and had little or no inhibitory effects on CYP enzyme activities.
"Changes in epigenetic regulation are present in all human cancers and act as the control center for a variety of cancer pathways," states Mike Clarke, MD PhD, one of the Founders of Tachyon Therapeutics. "TACH101 is able to halt cancer progression by blocking KDM4 which participates in a majority of these pathways. Being able to reverse these alterations at the core level has far-reaching implications for cancer prevention and treatment and we are looking forward to further explore the full potential of this drug candidate."

The poster presentation titled, "TACH101, a First-in-Class Pan-Inhibitor of KDM4 Histone Lysine Demethylases," is available for viewing on the AACR (Free AACR Whitepaper) Annual Meeting website at View Source!/9325/presentation/3226.

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.