On April 17, 2023 Myeloid Therapeutics, Inc. ("Myeloid"), a clinical stage mRNA-immunotherapy company, reported its presentation of two posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held in Orlando, Florida (Press release, Myeloid Therapeutics, APR 17, 2023, View Source [SID1234630199]).

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"At AACR (Free AACR Whitepaper) 2023, we are pleased to present late-breaking research on our in vivo engineering capabilities and clinical data from our Phase I IMAGINE study of MT-101 in PTCL patients," said Daniel Getts, Ph.D., Chief Executive Officer of Myeloid. "These data demonstrate the power of myeloid cells to orchestrate broad immune responses. We look forward to advancing our platform and expanding our clinical portfolio of in vivo programming candidates and ATAK CAR cell therapy candidates."

Details of the poster presentations are below:

Title: "In vivo delivery of novel CD89 fusion receptor to myeloid cells by mRNA activates anti-tumor immunity"
Session: Late-Breaking Research: Experimental and Molecular Therapeutics 1
Session Date and Time: Sunday April 16, 2023, 1:30 PM – 5:00 PM
Location: Poster Section 35
Poster Board Number: 19
Abstract Presentation Number: LB027

Abstract Highlights:

Myeloid illustrates with this poster its ability to engineer circulating and tumor-penetrating myeloid cells so that these cells are activated within the tumor setting and elicit anti-tumor adaptive immunity. This approach is an attractive, novel manner to harness systemic anti-tumor immunity.
Myeloid has applied its engineering insights to overcome challenges of specifically targeting and activating myeloid cells in vivo.
Myeloid has developed a novel in vivo myeloid cell engineering platform, in which a chimeric antigen receptor (CAR) is generated by fusing a tumor recognition scFv with the alpha chain of human Fc receptors (CD89). The stable expression and function of these receptors requires the endogenously expressed common Fc receptor gamma chain (FcRg), which expression is mostly restricted to myeloid cells.
For in vivo engineering, the construct is encapsulated and delivered in lipid nanoparticles (LNP).
Myeloid’s most-advanced in vivo programming candidate is a candidate referred to as MT-302, targeting trophoblast cell surface antigen 2 (TROP2) on cancer cells. TROP2 is overexpressed in most human solid epithelial cancers, as compared to low expression in corresponding normal tissue. Increased TROP2 expression has been linked to increased tumor growth and has been implicated as a prognostic marker in these cancers, supporting the development of earlier therapies targeting TROP2.
Within immunodeficient xenograft models of hepatocellular carcinoma and triple negative breast cancer, delivery of LNP mRNA encoding GPC3-CD89 or TROP2-CD89 fusion proteins resulted in anti-tumor efficacy, confirming the ability of this approach to program myeloid cells. Repeat dosing studies showed significant anti-tumor efficacy following bi-weekly administration of TROP2-CD89.
These studies highlight the potential of in vivo delivery of CD89 fusion proteins to program myeloid cells to recognize and kill cancer, thus providing a novel, promising approach to treating cancer.
Title: "Initial Preclinical and Clinical Experience of Autologous Engineered Monocytes in T cell Lymphoma Patients"
Session Category: Clinical Trials
Session: Phase I Clinical Trials in Progress
Session Date and Time: Monday April 17, 2023, 1:30 PM – 5:00 PM
Location: Poster Section 46
Poster Board Number: 19
Published Abstract Number: CT131

Abstract Highlights:

Myeloid developed the first engineered monocyte cell product, by engineering autologous monocytes to express a novel chimeric antigen receptor (CAR). This CAR contains a tumor recognition domain that is fused to a CD8 hinge domain, Fcγ and PI3K intracellular signaling domains. In addition to imparting tumor specificity, the Fcγ and PI3K signaling domains promote phagocytosis, cytokine production and antigen presentation upon activation.
In a rodent model of melanoma (gp75+ B16/F10-OVA), Ly6C+ monocytes engineered with this receptor were able to phagocytose tumor cells and cross present antigen in vitro. In vivo infusion of engineered monocytes was associated with significant suppression of tumor growth. FACS analysis of tumor-infiltrates demonstrated that engineered monocytes preferentially infiltrated tumors and differentiated into antigen presenting cells.
Based on these promising data, MT-101 is being assessed in humans in the Phase 1, open-label, first-in-human trial in patients with refractory or relapsed T cell lymphoma, IMAGINE trial (NCT05138458). The primary objective is the assessment of safety and tolerability at Day 28, following 3 weekly cycles of 2 infusions. Secondary objectives include assessment of correlative markers of response, pharmacokinetics, and efficacy.
In the first 3 subjects, MT-101 was well-tolerated, with no evidence of CRS, ICANS, or infusion reactions. Examination of biomarkers by CyTOF in one subject showed changes in circulating leukocytes, including B cells. In this subject, survival has been greater than 10 months, while the median overall survival of patients with R/R PTCL is 5.5 months.
Abstracts and full session details can be accessed through the AACR (Free AACR Whitepaper) meeting planner: AACR (Free AACR Whitepaper) Annual Meeting 2023 | Meetings | AACR (Free AACR Whitepaper).

About Myeloid’s ATAK CAR receptors and in vivo mRNA Programming

Myeloid’s novel class of CARs, known as ATAK Receptors, combine tumor recognition with multiple proprietary innate-immune signaling domains. Myeloid scientists have screened multiple unexplored combinations of innate-immune signals and uncovered optimal multi-signal pathways. The combination of cancer recognition binders with these novel intracellular signaling domains allows myeloid cells to be reprogrammed with previously unexplored combinations of immune signals, leading to tumor killing and broad systemic anti-tumor responses.

Myeloid’s novel in vivo engineering platform specifically targets and activates myeloid cells to elicit broader anti-tumor adaptive immunity. Through this approach, Myeloid demonstrates that delivery of lipid-nanoparticles (LNPs) encapsulating mRNA results in selective uptake and expression by myeloid cells in vivo, leading to potent tumor killing in multiple cold tumor models. These data demonstrate the potential for Myeloid’s technology to program cells directly in vivo.

On April 17, 2023 Shanghai Cellular Biopharmaceutical Group Ltd. (the Company, or Shanghai Cellular Bio), a company engaged in the drug development of immunotherapies for cancer and stem cell therapies for degenerative diseases, reported data from the First-in-Human (FIH) Phase I trial evaluating C-CAR031 at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Cellular Biomedicine Group, APR 17, 2023, View Source [SID1234630198]).

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Early results indicate that C-CAR031 is well tolerated with promising anti-tumor activity seen and objective responses in several patients to date, including 3 patients with confirmed partial responses, 2 with stable disease and 1 with progressive disease per both RECIST v1.1 and mRECIST criteria. The clinical responses of the patients who achieved partial responses are ongoing up to the data cutoff date.

C-CAR031 is an autologous GPC3-directed second generation armored CAR-T with affinity-tuned single-chain variable fragment (scFv) to enhance its safety profile, based on a novel cell therapy designed by AstraZeneca (LSE/STO/Nasdaq:AZN) using their TGFβRII dominant negative armoring discovery platform.

To investigate the feasibility, safety and initial efficacy of C-CAR301 in hepatocellular carcinoma (HCC), Shanghai Cellular Bio is currently conducting a Phase I FIH clinical study (NCT05155189) in advanced HCC in The First Affiliated Hospital, Zhejiang University School of Medicine in Hangzhou, China.

Poster Title:

"First report of preliminary safety, efficacy, and pharmacokinetics of
C-CAR031 (GPC3-specific TGFβRIIDN CAR-T) in patients with advanced HCC"

Session:

Session PO.CT01.01 – First-in-Human Phase I Clinical Trials 1

Poster No:

CT097

Date:

Monday, April 17, 2023

Time:

1:30 pm to 5:00 p.m. EDT

Location:

Orange County Convention Center in Orlando, Florida

Exhibit Halls Poster Section 45, Poster Board Number 5

Website:

View Source!/10828/presentation/10293

Methods: This FIH, open-label dose escalation trial employs an accelerated dose titration plus i3+3 design. Histologically confirmed GPC3+ advanced HCC patients (pts) who failed systemic treatments received a single-dose i.v. infusion of C-CAR031 following standard lymphodepletion. The primary objective was to assess the safety and tolerability. Adverse events (AEs) were graded using CTCAE 5.0, and cytokine release syndrome (CRS) / immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to ASTCT 2019 criteria.

Results: As of March 2nd, 2023, seven patients received two dose levels (DL1, n=1; DL2, n=6) of C-CAR031. The median number of prior lines of therapies was 4 (range 1-6). The median follow-up was 77 (67-213) days. Seven patients with ≥28 days’ follow-up were eligible for safety evaluation. Good safety profile was observed at explored dose levels. 86% (6/7) patients experienced Gr1/2 CRS; no Dose Limiting Toxicities (DLT) or ICANS was observed. The ≥Gr3 non-hematologic product-related AE included transient Gr3 AST elevation (2/7, 28%), hypokalemia (1/7, 14%), and abdominal pain (1/7,14%). 5/6 (83%) patients at DL2 showed tumor shrinkage post C-CAR031 treatment (median -41.4% range -3.4%~ – 94.4%). Best clinical responses at DL2 included 3 confirmed PR, 2 SD and 1 PD per both RECIST v1.1 and mRECIST. The clinical responses of the patients who achieved PR are ongoing up to the cutoff date. C-CAR031 showed a robust cellular kinetic profile. CAR-T cells were detectable in blood of all patients in the last follow-up.

Conclusion: In this FIH study, C-CAR031 is well tolerated and shows promising anti-tumor activity. Enrollment is ongoing to confirm initial results.

On April 17, 2023 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that it had released results from three preclinical studies of the company’s China-approved novel third-generation BCR-ABL inhibitor olverembatinib (HQP1351), and two key investigational apoptosis-targeted drug candidates of Ascentage Pharma, the Bcl-2 inhibitor lisaftoclax (APG-2575) and the MDM2-p53 inhibitor alrizomadlin (APG-115), in Poster Presentations at the 2023 American Association of Cancer Research Annual Meeting (AACR 2023; Orlando, FL) (Press release, Ascentage Pharma, APR 17, 2023, View Source;ascentage-pharma-presents-results-from-three-studies-underscoring-exploratory-efforts-in-potential-new-indications-301799608.htmlPress release [SID1234630197]).

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"The data we presented at this year’s AACR (Free AACR Whitepaper) Annual Meeting highlight the three drug candidates’ potential for clinical development and promising synergistic utilities in new indications," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "We will investigate these assets in the clinical setting and hope that these efforts will result in new therapeutic options for patients in need."

The details of these posters presented at AACR (Free AACR Whitepaper) 2023 are as follows:

Combination of olverembatinib (HQP1351) with Bcl-2 inhibitor lisaftoclax (APG-2575) overcomes resistance in gastrointestinal stromal tumors (GISTs)

Abstract#: 1631
Time: Monday, April 17, 2023, 9:00 AM-12:30 PM, EDT
GISTs are common malignant mesenchymal tumors that occur in the GI tract, with an estimated incidence rate of 1% to 2%. About 75% to 80% of patients with GIST have mutations in the KIT gene, while 5% to 10% have mutations in the platelet-derived growth factor receptor α (PDGFRA) gene. Tyrosine kinase inhibitors (TKIs) offer patients an improved quality of life, but increased pharmacological resistance to TKIs is often observed. Bcl-2 is expressed in >80% of GISTs, and amplification of Bcl-2 and Bcl-xL is a common feature associated with disease progression. One approach to GIST is to concurrently inhibit oncogenic KIT signaling while actively engaging apoptotic pathways. Olverembatinib (HQP1351) is a third-generation TKI that targets BCR-ABL1, KIT and PDGFRA and is currently in development for relapsed or refractory chronic myeloid leukemia and GIST. Lisaftoclax (APG-2575) is a selective Bcl-2 inhibitor under development for hematologic malignancies. The purpose of this study was to evaluate whether combining a Bcl-2 inhibitor, lisaftoclax, with olverembatinib enhances treatment effect on imatinib-resistant GISTs.
The results demonstrate that olverembatinib and Bcl-2 inhibitor lisaftoclax have synergistic antitumor effects in imatinib-resistant GIST. Considering that the resistance mechanisms are similar for most TKIs, this novel dual approach may have the potential for treating patients with GISTs whose disease has progressed after treatment with imatinib or other TKIs.
Olverembatinib (HQP1351) enhances antitumor effects of immunotherapy in renal cell carcinoma (RCC)

Abstract#：5071
Time: Tuesday, April 18, 2023, 1:30 PM-5:00 PM, EDT
In solid tumors, resistance to checkpoint inhibitors (CPIs) is frequently observed, partially due to upregulation of vascular endothelial growth factor A (VEGFA) and programmed death-ligand 1 (PD-L1) leading to an immunosuppressive tumor microenvironment and immune escape. Inhibitors against VEGF and the VEGF receptor (VEGFR) foster tumor vessel normalization and immunostimulatory reprogramming, in turn promoting treatment effects of immunotherapies. In recent years, tyrosine kinase inhibitors (TKIs) plus immunotherapy have been approved to treat advanced RCC. Olverembatinib is a third-generation multikinase inhibitor with targets including VEGFR, fibroblast growth factor receptor (FGFR), SRC, BCR-ABL1, c-KIT, and platelet-derived growth factor receptor (PDGFR). The drug is approved in China for the treatment of adult patients with TKI-resistant chronic phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation, and is currently under clinical development for relapsed or refractory CML and gastrointestinal stromal tumor. The aim of this study was to assess whether olverembatinib combined with immunotherapy can promote inhibitory effects on RCC.
The results demonstrate that combining olverembatinib with a CPI confers synergistic antitumor effects in an RCC mouse model by targeting tumor growth, angiogenesis, and immune regulation. This novel combination may provide an alternative approach to enhance treatment effects with CPIs in renal cancers.
MDM2 inhibitor alrizomadlin (APG-115) promotes antitumor activity of mitogen-activated protein kinase (MAPK) inhibitors in uveal melanoma

Abstract#：1632
Time: Monday, April 17, 2023, 9:00 AM-12:30 PM, EDT
Uveal melanoma (UM) is the most common primary intraocular malignancy, yet its molecular pathogenesis is poorly understood. Most UM cases have activating mutations in genes encoding G protein subunits alpha Q or 11, leading to activation of downstream effectors. These include protein kinase C, mitogen-activated protein kinases (MAPK1/3; also termed extracellular signal-regulated kinase 2/1 [ERK2⁄ERK1], respectively), and yes-associated protein, suggesting a rationale for therapeutically targeting these related pathways. Genetic analyses show that TP53 is infrequently mutated in UM, but associated pathways may be functionally inactivated. Ubiquitination-mediated degradation of p53 activates MAPK signaling such that active p53 may promote suppression of MAPK signaling. Alrizomadlin (APG-115) is a small molecule targeting p53/MDM2 that is in clinical development for solid and hematologic cancers. This study evaluated the antitumor effect of alrizomadlin, alone or combined with other targeted therapies, in preclinical models of UM.
The results demonstrate the potential utility of combining alrizomadlin with MAPK pathway inhibitors to treat patients with UM.

On April 17, 2023 Byondis B.V., an independent, clinical-stage Dutch biopharmaceutical company creating precision medicines, reported that the Journal for ImmunoTherapy of Cancer (the official journal of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)) has published encouraging preclinical data on its investigational monoclonal antibody (mAb) BYON4228 (Press release, Byondis, APR 17, 2023, View Source [SID1234630196]).

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BYON4228 targets and blocks the Cluster of Differentiation 47-Signal Regulatory Protein alpha (CD47-SIRPα) interaction responsible for tumors’ ability to escape recognition and destruction by the immune system. The Byondis paper, "BYON4228 is a pan-allelic antagonistic SIRPα antibody that potentiates destruction of antibody-opsonized tumor cells and lacks binding to SIRPγ on T cells," reports the findings of an extensive preclinical characterization of the novel SIRPα-directed antibody, including direct comparisons to previously reported anti-SIRPα antibodies. Side-by-side comparisons show that BYON4228 has a unique and favorable preclinical profile. The therapy is scheduled to enter First-in-Human (Phase I) study later this year. The Phase I clinical study (NCT05737628) is designed to evaluate BYON4228 alone and in combination with rituximab in patients with relapsed/refractory CD20-positive B-cell non-Hodgkin’s lymphoma.

Byondis Chief Scientific Officer Wim Dokter, Ph.D. explains: "BYON4228 is a pan-allelic antibody, meaning it recognizes the two major SIRPα variants in humans. In addition, because BYON4228 does not recognize SIRPγ, a related molecule on T cells, it should not compromise T cell activity."

"This implies that the therapy could benefit all eligible patients. Used in combination, BYON4228 can potentially increase the efficacy of a wide range of therapeutic mAbs in different blood and solid cancers," Byondis Chief Executive Officer Marco Timmers, Ph.D. added.

According to the published data, BYON4228 potentiates macrophage- and neutrophil-mediated killing of both hematologic and solid cancer cells in vitro in the presence of a variety of tumor-targeting antibodies, including trastuzumab, rituximab, daratumumab, panitumumab and cetuximab. In vivo, BYON4228 promotes the anti-tumor activity of such antibodies. Finally, BYON4228 shows a favorable preclinical safety profile.

More About BYON4228

BYON4228 is a humanized therapeutic monoclonal antibody designed to stimulate the innate immune system. It binds to SIRPα expressed on innate immune cells, especially monocytes, macrophages and neutrophils. BYON4228 blocks binding of SIRPα to CD47 (a cell surface molecule often over-expressed on cancer cells), preventing signaling through the CD47-SIRPα axis. The CD47-SIRPα axis limits the antibody-mediated destruction of cancer cells by transducing a "don’t eat me" signal to the immune system. By inhibiting the CD47-SIRPα axis, BYON4228 prevents the inhibitory "don’t eat me" signal to be detected, thereby stimulating the immune cell to do what it is supposed to do: destroy the tumor cell.

As a pan-allelic antagonistic SIRPα antibody that lacks binding to SIRPγ on T cells, BYON4228 has the potential to become best in class. It distinguishes itself from previously reported SIRPα antibodies that in all probability are representative of antibodies currently being tested in clinical trials.

On April 17, 2023 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading innovative, global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for cancer, reported the presentation of five posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 Meetings (AACR 2023), taking place from April 14th to 19th at the Orange County Convention Center in Orlando, Florida, the United States (Press release, Antengene, APR 17, 2023, View Source [SID1234630195]).

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"The five posters we present at AACR (Free AACR Whitepaper) 2023 provides Antengene with an opportunity to share a range of encouraging results including the expanded Phase II data of ATG-008 for the second-line treatment of patients with HBV+ HCC, as well as the preclinical results of ATG-017, ATG-037, ATG-031, and ATG-034,"said Dr. Bo Shan, Antengene’s Chief Scientific Officer. "A highlight of the results is the promising tumor response and overall survival data from the study in patients with advanced disease as they suggest that ATG-008 monotherapy represent a promising therapeutic option for patients who have received prior systemic therapy, including PD-1/PD-L1 inhibitors. Maintaining our focus on addressing patients’ unmet clinical needs, we will continue to actively explore and evaluate combinations between our existing programs and other targets and agents, with the hope of gathering sufficient rationale to support the future clinical development of these regimens."

Details of the Poster Presentations:

ATG-008 (mTORC1/2 inhibitor)

Title: Result of an open-label phase 2 trial of dual TORC1/TORC2 inhibitor onatasertib(ATG-008) in HBV+ advanced hepatocellular carcinoma(HCC) subjects who have received at least one prior line of systemic therapy(TORCH)

Abstract: CT150

Date: April 17, 2023

Time: 1:30 PM – 5:00 PM (Eastern Time)
1:30 AM – 5:00 AM, April 18, 2023 (Beijing Time)

This Phase II study was designed to evaluate the pharmacokinetics, safety and efficacy of ATG-008 in patients with advanced hepatitis B virus (HBV) positive hepatocellular carcinoma (HCC). 73 patients with HBV+, unresectable and refractory HCC were enrolled to receive ATG-008 at one of the four dose levels.
Data from this study showed that 3 subjects achieved a partial response (PR), all in the 45 mg QD monotherapy cohort. A total of 18 patients were enrolled in this cohort that achieved an objective response rate (ORR) of 16.7%. Among them, 11 patients (61.1%) had received at least 2 prior lines of therapy and 15 patients had been exposed to an anti-PD-1/PD-L1 checkpoint inhibitor (CPI) (83.3%). The median progression-free survival (mPFS) was 3 months in the intend-to-treat (ITT) population and 5.3 months in the 45mg QD cohort.
These data suggest that ATG-008 has single-agent efficacy in HBV+ HCC patients who have failed at least one prior systemic therapy, notably in the 45 mg QD dosing level, in which most patients had been previously exposed to an anti-PD-1/PD-L1 therapy. Further, the results indicate that ATG-008 has the potential in HBV+ HCC patients who have failed prior CPI therapy and support further study, particularly in patients who have failed prior anti-VEGF and anti-PD-l/PD-L1 therapy. ATG-008 is being evaluated in the Phase II TORCH-2 study in patients with cervical cancer and other solid tumors.
ATG-017 (ERK1/2 inhibitor)

Title: Synergistic effects of the combination of ERK1/2 with EGFR, KRASG12C, CDK4/6, and PD-L1 inhibition for cancer treatment

Abstract: 5499

Date: April 18, 2023

Time: 1:30 PM – 5:00 PM (Eastern Time)

1:30 AM – 5:00 AM, April 19, 2023 (Beijing Time)

This preclinical study was designed to test the in vivo anti-tumor effects induced by the combination of ATG-017, with EGFR inhibitor (osimertinib), KRASG12C inhibitor (ATG-012), CDK4/6 inhibitor (abemaciclib) or PD-L1 inhibitor (atezolizumab), in preclinical tumor models including three models of non-small cell lung cancer (NSCLC) (with EGF-R and KRAS mutations), and one model of T-cell lymphoma (resistant to anti-PD-L1) for assessing the tumor growth inhibition (TGI) and the presence of tumor infiltrating lymphocytes (TILs).
According to the results, ATG-017 demonstrated significant TGI (>60%) in the NSCLC models. In the T-cell lymphoma model, the combination of ATG-017 and the PD-L1 inhibitor, atezolizumab, showed significant tumor growth inhibition. Furthermore, that combination induced increased the infiltration of anti-tumor TILs, suggesting a potential role for ATG-017 in changing "cold" tumors to "hot".
These data suggest that the combination of ATG-017 with EGFR, KRASG12C, CDK4/6, and PD-L1 inhibitors have strong synergism and significantly improved TGI, thus represent promising therapeutic strategies for cancer patients. Antengene is evaluating ATG-017 in the Phase I ERASER study, as monotherapy and in combination with nivolumab, in patients with advanced solid tumors and hematological malignancies in Australia and the U.S.
ATG-037 (CD73 inhibitor)

Title: Targeting CD73-Adenosine Axis for the treatment of multiple myeloma

Abstract: 496

Date: April 16, 2023

Time: 1:30 PM – 5:00 PM (Eastern Time)

1:30 AM – 5:00 AM, April 17, 2023 (Beijing Time)

This preclinical study was designed to evaluate the potential of ATG-037 in treating multiple myeloma (MM). CD73 is a cell surface enzyme which is highly expressed in the tumor microenvironment and enables the conversion of ATP to adenosine, promoting the progression of cancer by inhibiting T-cells, natural killer (NK) cells, and dendritic cells (DCs), and inducing and enhancing the function of immunosuppressive cell types. ATG-037’s ability to inhibit the activity of CD73 was evaluated in enzyme inhibition and T cell proliferation and activation assays. In vivo efficacy was assessed in syngeneic myeloma models.
Results showed complete inhibition of CD73 with ATG-037, without a "hook effect" compared to another industry benchmark antibody program. In addition, ATG-037 completely restored the function of activated T-cells and CAR-T cells from AMP-mediated T-cell suppression, suggesting a potential application in CAR-T cell therapy. In addition, the treatment with ATG-037 resulted in significant TGI compared to vehicle controls.
These data suggest that ATG-037 has single agent anti-myeloma efficacy, thus making this abstract the first report of in vivo efficacy study of a CD73 inhibitors in myeloma animal models. Antengene is currently evaluating ATG-037 in Australia and mainland of China in the Phase I STAMINA study, as a monotherapy and in combination with pembrolizumab, in patients with locally advanced or metastatic solid tumors.
ATG-031 (anti-CD24 monoclonal antibody)

Title: ATG-031, a first-in-class humanized anti-CD24 antibody, demonstrates potent in vivo efficacy and repolarizes tumor-associated macrophages in the TME

Abstract: 6641

Date: April 19, 2023

Time: 9:00 AM – 12:30 PM (Eastern Time)

9:00 PM April 19 – 12:30 AM April 20, 2023 (Beijing Time)

This preclinical study was designed to evaluate the in vivo efficacy of ATG-031 and explored its pharmacodynamic effects.
Data showed that ATG-031 monotherapy produced robust, 60-100% TGI, with increased, synergistic tumor regression from the combination of ATG-031 with oxaliplatin (chemotherapy) or atezolizumab (CPI), evaluated in one of the murine models. Flow cytometry analysis shows that ATG-031 increases T cell (CD4/CD8) tumor infiltration and significantly lower population of Treg cells in the tumor microenvironment.
These results suggest that the first-in-class antibody, ATG-031, specifically binds to CD24 with nM affinity and blocks the interaction of CD24 and Siglec-10. ATG-031 induces efficient phagocytosis with a picomolar EC50, stimulating pro-inflammatory cytokines production by macrophages.
ATG-034 (LILRB4 antagonist antibody)

Title: ATG-034, an LILRB4 antagonist antibody, reinvigorates dendritic cells and prevents tumor progression

Abstract: 6384

Date: April 19, 2023

Time: 9:00 AM – 12:30 PM (Eastern Time)

9:00 PM April 19 – 12:30 AM April 20, 2023 (Beijing Time)

This preclinical study was designed to evaluate ATG-034, an antibody targeting LILRB4, as a potential immunotherapy. The antibody was tested using SPR, ELISA and FACS analysis to assess its ability to bind to LILRB4, block its interaction with its ligand, fibronectin, and reinvigorate DCs to an "immunogenic" state.
According to the data, ATG-034 demonstrated single-digit nanomolar affinity and blocked the interaction of LILRB4 with its target ligand, fibronectin and completely reversed fibronectin-mediated suppression of tolerized DC activation (TolDC), evidenced by increased TNF-a production. In addition, the antibody reprogrammed DCs to become immunogenic, as measured by the up regulation of several key co-stimulatory molecules (CD86, HLA-DR and HLA-ABC) and down-regulation of an M2 biomarker (CD206).
These results suggest that ATG-034 successfully reprogrammed tolerized DCs to an "immunogenic" state, thereby enhancing anti-tumor immunity and demonstrating potent in vivo anti-tumor efficacy compared to a benchmarking compound.