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.

On April 10, 2021 Ultimovacs ASA ("Ultimovacs", ticker ULTI), reported that it is presenting a poster today on the trial design of its ongoing Phase II INITIUM clinical study evaluating nivolumab and ipilimumab in combination with the Company’s proprietary universal cancer vaccine, UV1, as first line treatment in patients with metastatic malignant melanoma, at the 2021 AACR (Free AACR Whitepaper) Annual Meeting, held virtually from April 9 to April 14, 2021 (Press release, Ultimovacs, APR 10, 2021, View Source [SID1234577869]).

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The poster, titled, "Nivolumab and ipilimumab +/- UV1 vaccine as 1st line treatment in patients with malignant melanoma (INITIUM-trial)", details the INITIUM study, a randomized, open label study investigating the efficacy and safety of UV1 vaccination in combination with nivolumab and ipilimumab as first line treatment in histologically confirmed unresectable metastatic melanoma patients. The INITIUM study is enrolling 154 patients, randomly assigned to the experimental arm or the control arm. Patients in the experimental arm will receive 8 UV1 vaccinations over 4 cycles of nivolumab and ipilimumab, whereas patients in the control arm will receive 4 cycles of nivolumab and ipilimumab without UV1 vaccination. In both arms, patients will start maintenance therapy with nivolumab after the last dose of induction therapy and will be followed until the end of the study. The primary outcome of the study is the Progression Free Survival (PFS) of patients in the experimental arm compared to patients in the control arm. Secondary outcomes include the comparison of Overall Survival (OS) and Objective Response Rate (ORR) between the groups.

Details of the presentation are as follows:

Title:

Nivolumab and ipilimumab +/- UV1 vaccine as 1st line treatment in patients with malignant melanoma (INITIUM-trial)

Session Type:

E-poster Session

Session Title:

Phase II Clinical Trials in Progress

Abstract Number:

CT23

The poster is available on Ultimovacs’ corporate website at www.ultimovacs.com.

On April 10, 2021 Synlogic, Inc. (Nasdaq: SYBX), a clinical stage company bringing the transformative potential of synthetic biology to medicine, reported data on SYNB1891 for the treatment of solid tumors and lymphoma during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, April 10-15, 2021 (Press release, Synlogic, APR 10, 2021, View Source [SID1234577821]).

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The presentation, "Intratumoral injection of SYNB1891, a Synthetic Biotic designed to activate the innate immune system, demonstrates target engagement in humans including intratumoral STING activation," was delivered by Dr. Filip Janku, Associate Professor, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. The presentation recording will be available throughout the duration of the conference.

SYNB1891 is an investigational drug being evaluated in an ongoing Phase 1 clinical trial for the treatment of solid tumors and lymphoma. SYNB1891 is composed of an engineered Synthetic Biotic strain of E. coli Nissle that produces cyclic di-AMP (CDA), a stimulator of the STING (STimulator of INterferon Genes) pathway. This mechanism can play a critical role in the initiation of an anti-tumor immune response via activation of APCs and presentation of tumor antigens. Findings from the monotherapy cohorts include:

SYNB1891 is safe and well-tolerated as an intratumoral injection in a heterogenous population.
No dose limiting toxicities or SYNB1891-related infections
Dose levels through 1e7 live cells demonstrate target engagement as assessed by dose-dependent increases in serum cytokines, upregulation of ISGs and presence of tumor infiltrating lymphocytes.
Evidence of durable stable disease was seen in 2 patients and was associated with upregulation genes tied to immune activation and increased intratumoral lymphocytes.
These data support continued dose escalation in the monotherapy and combination arms. The combination arm of the study combines escalating dose levels of SYNB1891 with a fixed dose of a PD-L1 checkpoint inhibitor antibody to establish a recommended Phase 2 dose for the combination regimen.

Data from both arms will continue to be reported over the course of 2021, with mature combination therapy data expected by the end of the year.

Learn more about Synlogic’s programs and pipeline by visiting View Source

About SYNB1891
SYNB1891 is an investigational drug for the intra-tumoral treatment of solid tumors and lymphoma, composed of an engineered Synthetic Biotic strain of E. coli Nissle that produces cyclic di-AMP (CDA), a stimulator of the STING (STimulator of INterferon Genes) pathway. This mechanism can play a critical role in the initiation of an anti-tumor immune response via activation of APCs and presentation of tumor antigens. The bacterial chassis of SYNB1891 also stimulates the innate immune system by several other mechanisms, including via Toll-like receptors (TLRs), potentially adding to the magnitude of the overall immune response. While SYNB1891 has been engineered with safety features that are designed to prevent its replication unless supplemented with specific nutrients, the bacteria remain active for several days within the injected tumor to stimulate a local immune response. SYNB1891 is being evaluated in a Phase 1 clinical trial (NCT04167137).

On April 10, 2021 Arch Oncology, Inc., a clinical-stage immuno-oncology company focused on the discovery and development of anti-CD47 antibody therapies, reported the presentation of new preclinical data on AO-176 in pediatric acute lymphoblastic leukemia (T-ALL) during a late-breaking poster presentation at the AACR (Free AACR Whitepaper) Annual Meeting 2021 (Press release, Arch Oncology, APR 10, 2021, View Source;utm_medium=rss&utm_campaign=arch-oncology-presents-new-preclinical-t-all-data-on-highly-differentiated-anti-cd47-antibody-ao-176-at-aacr-2021 [SID1234577838]). This research was funded by a grant from the National Cancer Institute (NCI), part of the National Institutes of Health, to the Pediatric Preclinical Testing Consortium (PPTC).

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AO-176 is an anti-CD47 antibody with a potential best-in-class profile that works by blocking the "don’t eat me" signal and also by directly killing tumor cells, with preferential binding to tumor versus normal cells. Currently, AO-176 is being evaluated in Phase 1/2 clinical trials for the treatment of patients with select solid tumors and hematologic malignancies, both as monotherapy and in combination with standard therapies.

"At AACR (Free AACR Whitepaper) this year, we are presenting preclinical data in two new hematologic indications, showing AO-176’s strong therapeutic potential in lymphoma and pediatric T-ALL," said Daniel Pereira, Ph.D., Chief Scientific Officer of Arch Oncology. "AO-176 demonstrated significant single-agent in vivo anti-leukemic activity in pediatric T-lineage ALL PDX models. Our antibody delayed disease progression and decreased human leukemia infiltration of murine spleens to increase overall survival in mice inoculated with T-ALL cells, suggesting that targeting CD47 in T-ALL may be a promising therapeutic approach. AO-176 has highly-differentiated mechanisms that show the potential to offer an improved efficacy and safety profile among anti-CD47 agents in development for patients and we are excited to continue to advance this novel therapy in the clinic for patients with solid tumors and hematologic malignancies."

Richard Lock, Ph.D., Lead Investigator for this study and Head of the Blood Cancers Theme and Group Leader of the Leukaemia Biology Group at Children’s Cancer Institute, one of the NCI funded PPTC institutions, added "AO-176 exhibited impressive single-agent in vivo activity for a monoclonal antibody against highly-aggressive experimental models of pediatric T-cell acute lymphoblastic leukemia. Given its novel mechanisms of action and single-agent activity, there is great interest in next testing AO-176 in combination with standard-of-care drugs against experimental models of high-risk pediatric leukemia."

American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021

Late-Breaking Poster Presentation Title: The differentiated CD47 monoclonal antibody AO-176 exhibits significant in vivo activity against xenograft models of pediatric acute lymphoblastic leukemia (ALL) (Abstract # LB171)
Session Category: Immunology
Session Title: Therapeutic Antibodies, Including Engineered Antibodies

Poster Presentation Title: AO-176, a highly differentiated clinical stage anti-CD47 antibody, is efficacious in pre-clinical models of lymphoma (Abstract #954)
Session Category: Experimental and Molecular Therapeutics
Session Title: Biological Therapeutic Agents

Information on the abstracts is available on AACR (Free AACR Whitepaper)’s website.

These poster presentations are available at View Source

About AO-176

AO-176 is a humanized anti-CD47 IgG2 antibody with a potential best-in-class profile. AO-176 is highly differentiated, with the potential to improve upon the safety and efficacy profile relative to other agents in this class of innate checkpoint inhibitors. AO-176 is engineered to block the "don’t eat me" signal, the standard mechanism of anti-CD47 antibodies. Beyond blocking this signal, AO-176 has additional mechanisms, including directly killing tumor cells and inducing DAMPs (damage associated molecular patterns) in preclinical models, resulting in immunogenic cell death. Importantly, in these models AO-176 binds preferentially to tumor cells, instead of to normal cells, and binds even more potently to tumors in their acidic microenvironment (low pH). Publications and presentations on AO-176 can be found at View Source

AO-176 is being evaluated in Phase 1/2 clinical trials for the treatment of patients with select solid tumors and hematologic malignancies, both as monotherapy and in combination with standard therapies. In a Phase 1 trial in solid tumors, AO-176 demonstrated encouraging early tolerability and activity when administered as a single agent. Additional information about these trials may be found at www.clinicaltrials.gov using the trial identification number NCT03834948 (solid tumors) or NCT04445701 (multiple myeloma).

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.