On November 12, 2021 CERo Therapeutics, Inc., a biopharmaceutical company pioneering the development of novel autologous engineered immune cell therapies, reported the results from preclinical in vitro studies describing the characterization of novel chimeric engulfment receptor (CER) T cells (Press release, Cero Therapeutics, NOV 12, 2021, View Source [SID1234595466]). CERs are genetically engineered proteins that bind to tumor-agnostic, inducible stress ligands on the surface of tumor cells to provoke tumor-specific cytotoxicity and innate immune functions such as engulfment and antigen presentation. The data, which are being presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2021), demonstrate that T cells engineered to express CERs exhibit multifunctional properties of both innate and adaptive immune responses and suggest the potential for CER T cells to overcome barriers associated with existing adoptive cell-based therapies.

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"These studies highlight for the first time the unique orthogonal profile of CER T cells to combine the tumor cell clearance attributes of macrophages and dendritic cells of the innate immune system with the T-cell activation of the adoptive immune system into a single engineered T cell," said Daniel Corey, MD, founder and CEO of CERo. "One of the limitations of activated T cells is their poor ability to present antigens due to inefficient antigen capture. In contrast, CER T cells facilitate antigen capture, processing and presentation, and impart target-dependent cytokine function, thereby offering a possible means of improving the therapeutic potential of engineered cell therapies."

In the studies, CER T cell constructs containing an extracellular phagocytic receptor were characterized for multiple functions, including cytotoxicity in combination with a Bruton’s tyrosine kinase inhibitor (BTKi), tumor cell fragment uptake, T-cell activation, cytokine induction, and antigen-presenting cell (APC)-like activity. Results of these in vitro studies showed that CER T cells synergized with a BTKi to enhance killing of a mantle cell lymphoma tumor cell line. Further, CER T cells exhibited abilities to capture tumor cell fragments and induce expression of T-cell activation markers and cytokines. CER T cells containing a toll-like receptor (TLR) domain also showed enhanced ability to present exogenous antigen and activate antigen-specific TCR T cells.

The poster entitled "Enhanced antigen capture, antigen-presenting cell (APC)-like function, and cytotoxic responses with chimeric engulfment receptor (CER) T cells" (Abstract #207) is now accessible virtually via the SITC (Free SITC Whitepaper) website and in person today from 7:00 a.m. – 8:30 p.m. ET in Exhibit Hall E.

About CERo’s Platform Technology

CERo’s technology aims to expand the therapeutic potential of engineered T cell-based therapies by introducing distinct and complementary tumor cell clearance pathways into a single T cell. By engineering T cells to express CERs, CERo’s platform technology enables T cells to target tumors, induce cellular damage, engulf tumor fragments, and clear tumors, effectively harnessing the anti-tumor attributes of both innate and adaptive immune responses. CER T-cell products are designed to generate a more complete and durable anti-tumor response. This novel biology amends itself to combinations with classic CAR T-cell or small molecule therapy and has potential applications in hematologic malignancies and solid tumors.

On November 12, 2021 Sierra Oncology, Inc. (NASDAQ: SRRA), a late-stage biopharmaceutical company on a mission to deliver targeted therapies that treat rare forms of cancer, reported the company will participate in the 2021 Jefferies London Healthcare Conference (Press release, Sierra Oncology, NOV 12, 2021, View Source [SID1234595465]). Stephen Dilly, MBBS, PhD, President and Chief Executive Officer of Sierra, will provide an overview of the company in a presentation that will be available on demand beginning at 8:00 am GMT (3:00 am ET) on Thursday, November 18, 2021, to conference attendees.

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A replay of the presentation will be available following the conference on the Investors section of Sierra’s corporate website in the Events & Webcast tab. The replay will be available for approximately 30 days following the presentation.

On November 12, 2021 MiNA Therapeutics Limited ("MiNA" or the "Company"), the pioneer in small activating RNA (saRNA) therapeutics, reported that positive safety data from the Phase 1a/b TIMEPOINT study of MTL-CEBPA in combination with pembrolizumab in adult patients with advanced solid tumours (Press release, MiNA Therapeutics, NOV 12, 2021, View Source [SID1234595464]). The data will be initially presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, taking place on 10-14 November 2021. Separately, MiNA also highlights the publication of positive data in the peer-reviewed journal Clinical Cancer Research, demonstrating MTL-CEBPA’s mechanism of action across different tumour models and in cancer patients.

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Robert Habib, CEO of MiNA Therapeutics, commented:

"The data presented at SITC (Free SITC Whitepaper) and published in Clinical Cancer Research further adds to the strong foundation of clinical evidence we have established for MTL‑CEBPA. Multiple studies across different tumour models and in cancer patients have demonstrated the unique immunological effects of MTL-CEBPA and its role as a potential combination treatment in cancer. We are excited to progress into Phase 1b the development of MTL-CEBPA in patients with solid tumour malignancies."

Data presented at SITC (Free SITC Whitepaper) from the ongoing Phase 1a/b, first-in-human, open-label, multicenter TIMEPOINT study demonstrates the safety and tolerability of MiNA’s lead candidate, MTL-CEBPA in combination with pembrolizumab, an approved anti-PD-1 (programmed death receptor-1) checkpoint inhibitor. The study is enrolling patients with advanced solid tumour treatment settings in which anti-PD-1 checkpoint inhibitors are not approved therapies.

At the three dose levels tested, the combination was generally well tolerated, with no dose-limiting toxicity and no serious adverse events observed. Encouragingly, anti-tumour activity was also observed in three patients. These included two confirmed partial responses in patients with advanced ovarian cancer and malignant pleural mesothelioma. The data package to date supports the continuation of this programme and MiNA is currently enrolling patients into a Phase 1b dose expansion cohort, which will additionally assess immunological changes as well as clinical activity of the combination treatment. Analysis of approximately 40 patients in the Phase 1b dose expansion cohort is expected to complete in the second half of 2023.

Additionally, translational proof-of-concept data further establishing MTL-CEBPA’s mechanism of action was recently published in the peer-reviewed journal Clinical Cancer Research. The data demonstrated that therapeutic up-regulation of C/EBP-α by MTL-CEBPA caused inactivation of immune-suppressive myeloid cells, potentiating anti-tumour responses in patients with advanced primary liver cancer (hepatocellular carcinoma (HCC)), as well as in several pre-clinical tumor models, including liver cancer, lung carcinoma, and colon adenocarcinoma.

This data provides evidence to support the role of MTL-CEBPA to counteract a key cancer immune evasion pathway by inhibiting immune suppression by myeloid cells, and for the potential of MTL‑CEBPA in combination treatment with immunotherapies across multiple tumour types. This data also supports MiNA’s strategy in liver cancer, where the Company is investigating MTL-CEBPA in patients with advanced HCC in combination with sorafenib (standard-of-care multi-kinase inhibitor), with a randomised Phase 2 clinical trial (OUTREACH-2) expected to initiate around the end of 2021.

Both the poster presented at SITC (Free SITC Whitepaper) and paper published in Clinical Cancer Research will be made available on the Company’s website in the Publications section under "RNA Activation".

About the TIMEPOINT study

TIMEPOINT is a global Phase 1a/1b clinical study in patients with solid tumour malignancies that will assess the safety and tolerability of MTL‑CEBPA in combination with pembrolizumab in patients who are ineligible or resistant to standard therapies. The study has received clearance from the U.S. Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). To learn more about the TIMEPOINT clinical study, please visit our listing at clinicaltrials.gov.

About MTL-CEBPA

MTL-CEBPA is the first therapy that specifically up-regulates CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of myeloid cell lineage determination and differentiation. Dysregulated myeloid cells have been implicated in several diseases and in solid tumour cancers have been identified as a critical barrier for many therapies to induce clinical responses. In pre-clinical studies MTL-CEBPA has been shown to improve the anti-tumour activity of cancer therapies by targeting dysregulated myeloid cells and reducing their suppressive effect in the tumour micro-environment. MTL-CEBPA is currently in clinical development as a combination therapy for the treatment of advanced liver cancer and advanced solid tumour malignancies.

On November 12, 2021 MiNA Therapeutics Limited ("MiNA" or the "Company"), the pioneer in small activating RNA (saRNA) therapeutics, reported that its Chief Executive Officer, Robert Habib, will present and host one-on-one meetings at the Jefferies 2021 London Healthcare Conference, taking place from 16-19 November 2021 in-person and virtually (Press release, MiNA Therapeutics, NOV 12, 2021, View Source [SID1234595463]).

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MiNA’s presentation will take place at 3:40pm GMT on Tuesday, 16 November 2021, with a live webcast available via the following link: View Source

Mr Habib will introduce MiNA and its saRNA technology platform, as well as provide an update on the Company’s clinical progress and strategy.

On November 12, 2021 Bicara Therapeutics, a clinical-stage biotechnology company developing dual-action biologics designed to elicit a potent and durable immune response in the tumor microenvironment, reported that a poster highlighting promising new preclinical data for BCA101, a bifunctional antibody designed to localize the TGF-β trap to EGFR+ tumors currently in an ongoing Phase 1/2 study, will be presented on Saturday, November 13, 2021 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2021 Annual Meeting in Washington, D.C (Press release, Bicara Therapeutics, NOV 12, 2021, View Source [SID1234595462]).

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"These data show that BCA101, our first-in-class bifunctional antibody, has strong potential to improve anti-tumor response versus historical EGFR inhibitors by leveraging the interplay between the EGFR and TGF-β signaling pathways. It also suggests synergy in combination with PD-1 inhibitors with the potential to delay and overcome PD-1 resistance," said Liviu Niculescu, M.D., Chief Medical Officer of Bicara Therapeutics. "These preclinical data are very encouraging for our ongoing clinical trial aimed at giving cancer patients a treatment option with better efficacy and safety than currently available options. We look forward to reporting data from the Phase 1/2 clinical trial in the second half of 2022."

Details of the poster are as follows:

Title: Development of BCA101, a Bifunctional Antibody Capable of Simultaneously Disabling EGFR and TGF-β Signaling, as a Novel Single-agent Immunotherapy
Poster Number: 874
Category: Novel Single-Agent Immunotherapies
Presentation Date and Time: Friday, November 12, 2021, at 7:00 a.m.
Authors: Srinivas R. Boreddy, Ph.D.; Reshmi Nair; Arindam Banerjee; Anshu Kuriakose; Prashant Kumar Pandey; Chaitali Dey; Meena Shri; Shruthi Rao; Bhadravathi Marigowda Shivakumar; Moni Abraham Kuriakose; Ram Bhupal Reddy; Amrita Suresh; Praveen Reddy Moole; Usha Bughani; Seng-Lai Tan, Ph.D.; Pradip Nair

Key findings:

Improved retention of BCA101 in tumor microenvironment compared to TGF-bRII-Fc alone
BCA101 inhibits TGF-β-induced epithelial to mesenchymal transition and rescues from TGF-β-mediated immune inhibition
BCA101 demonstrates superior anti-tumor efficacy compared to cetuximab + TGF-bRII-Fc in vivo
BCA101 demonstrates sustained tumor regression compared to cetuximab in HNSCC-PDX models
BCA101 exhibited improved efficacy in combination with anti-PD-1 inhibitor in checkpoint-resistant HuNOG-EXL humanized model
BCA101 is currently being evaluated in a Phase 1/2 study as both a monotherapy in patients with EGFR-driven tumors and in combination with pembrolizumab (anti-PD-1) in squamous cell carcinoma of the head and neck (SCCHN) and squamous cell carcinoma of the anal canal (SCCAC). The study is currently enrolling patients in dose escalation and will open dose expansions in 2022.

About BCA101

BCA101 is a first-in-class EGFR / TGF-β-trap bifunctional antibody designed to enhance both innate and adaptive immune responses directly at the site of the tumor by binding to the well-validated EGFR antigen and disabling TGF-β, a signaling molecule that plays a key role in suppressing the immune response in the tumor microenvironment. Promising preclinical data suggest that BCA101 is superior to the anti-EGFR antibody cetuximab in preventing tumor recurrence, as well as in restoring immune activation. An ongoing Phase 1/2 clinical trial of BCA101, initiated in July 2020, has dosed the first six cohorts of patients in a dose-escalation study with BCA101 as a single agent. A second arm of the study began enrolling patients for combination treatment with BCA101 and pembrolizumab, a PD-1 inhibitor, in January 2021. For more information, please visit www.clinicaltrials.gov.