On November 9, 2020 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company engineering a novel class of injectable biologics to selectively engage and modulate targeted T cells within the patient’s body, reported three poster presentations highlighting the Company’s clinical and pipeline progress at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 35th Anniversary Annual Meeting (SITC 2020) (Press release, Cue Biopharma, NOV 9, 2020, View Source [SID1234608293]). The posters include a clinical update on CUE-101, the lead drug candidate from the IL-2 based CUE-100 series, and data supporting the potential of the Immuno-STAT (Selective Targeting and Alteration of T cells) platform to selectively engage and modulate targeted T cells within the body in a manner that can address a broad range of indications.
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"We are pleased to share data providing further supportive evidence of the potential benefits of our Immuno-STAT platform throughout its stages of development," said Anish Suri, Ph.D., president and chief scientific officer of Cue Biopharma. "We are encouraged by the dose-proportional signals and metrics of clinical activity as well as the tolerability observed in our ongoing Phase 1 trial of CUE-101, as we continue enrollment with the next incremental level of dosing. Our preclinical data demonstrate the potential versatility and modularity of the Immuno-STAT platform for a wide array of indications, including the potential for prognostics and diagnostics, with evidence of localization and engagement with disease-relevant T cells, as well as activation and expansion."
Due to the abstract submission and acceptance dates for SITC (Free SITC Whitepaper), the poster highlighting progress on CUE-101 will only contain data updates through cohort 4. Members of the Cue Biopharma executive management team will provide further updates and details pertaining to patients from cohorts 4, 5 and 6 at the upcoming quarterly update call on November 17 at 4:30 p.m. EST. In addition, Cue Biopharma has recently received permission from the Clinical Safety and Review Committee to proceed with dose escalation to cohort 7 at 8 mg/kg.
The SITC (Free SITC Whitepaper) Presentations include:
A phase 1 trial of CUE-101 a novel HPV16 E7-pHLA-IL2-Fc fusion protein in patients with recurrent/metastatic HPV16+ head and neck cancer (Abstract #354)
Presenter: Sara I. Pai, M.D., Ph.D., associate professor, Massachusetts General Hospital and Harvard Medical School, Boston
An ongoing multicenter, open-label, dose escalation Phase 1 trial is evaluating the safety, tolerability, anti-tumor response, pharmacokinetics and immunogenicity of CUE-101 as a monotherapy in patients with confirmed human papilloma virus positive recurrent/metastatic head and neck squamous cell carcinoma (HPV+ HNSCC) and HLA-A*02:01 serotype (NCT03978689). Results from 19 participants who have received CUE-101 at doses ranging from 0.06 to 1 mg/kg demonstrate acceptable tolerability, favorable pharmacokinetics (PK) and preliminary pharmacodynamics (PD) signals that indicate selective activation of tumor-specific T cells, enabling dose escalation to the next level (2 mg/kg).
CUE-100 series Immuno-STATs from concept to the clinic: Leveraging protein engineering to stimulate and selectively deliver affinity-attenuated IL-2 to antigen-specific T cells (Abstract #553)
Presenter: Saso Cemerski, Ph.D., vice president and head, discovery and translational immunology, Cue Biopharma
In vitro and in vivo evaluation of CUE-100 series Immuno-STATs specific to different antigenic peptides demonstrated expansion of functional, oligoclonal, antigen-specific T cell repertoires with functional attenuation of the IL-2 components. CUE-100 series Immuno-STATs administered to human peripheral blood mononuclear cells (PBMCs) selectively activated and expanded antigen-specific CD8+ T cells after primary stimulation and re-stimulation with antigenic peptides from HPV16, Wilms’ tumor 1 (WT1), melanoma antigen recognized by T cells 1 (MART-1), cytomegalovirus (CMV), influenza and HIV. In naïve HLA-A*02 transgenic mice, CUE-100 series Immuno-STATs expanded CD8+ T cells, exhibiting a polyfunctional response upon challenge with peptide-presenting target cells.
Immuno-STATs: Leveraging protein engineering to expand and track antigen-specific T cells in vivo (Abstract #623)
Presenter: Steven Almo, Ph.D., co-founder, Cue Biopharma
The potential modularity of the Immuno-STAT platform and ability to selectively deliver costimulatory, coinhibitory or cytokine signals and other modalities to primary T cells of defined specificity was observed through the use of a novel immuno-positron emission tomography (PET) imaging approach. PET-active radiolabels were installed on dimeric protein scaffolds comprising the core structure of the Immuno-STAT to visualize the in vivo localization of antigen-specific T cells. Results showed that HPV16-specific CD8+ T cells were localized to implanted HPV16-positive tumors in mice, and influenza A virus (IAV)-specific CD8+ T cells were localized to the lungs of IAV-infected mice. HIV- and CMV-specific Immuno-STATs administered to immunodeficient mice intrasplenically engrafted with human PBMCs resulted in selective expansion of disease-relevant T cells in the spleen. These data represent the first report of the in vivo imaging of antigen-specific CD8+ T cell populations and in vivo antigen-selective expansion of human CD8+ T cells, which suggests the presence of Immuno-STAT biologics in the particular tumor or infected tissues where they act, eliciting selective activation and expansion of target T cells. These results suggest that, in addition to broad therapeutic applications, Immuno-STATs may also provide prognostic and diagnostic information.
For more information on all three posters please visit: https://bit.ly/3k4HymQ.
About the CUE-100 Series
The CUE-100 series consists of Fc-fusion biologics that incorporate peptide-MHC (pMHC) molecules along with rationally engineered IL-2 molecules. This singular biologic is anticipated to selectively target, activate and expand a robust repertoire of tumor-specific T cells directly in the patient. The binding affinity of IL-2 for its receptor has been deliberately attenuated to achieve preferential selective activation of tumor-specific effector T cells while reducing potential for effects on regulatory T cells (Tregs) or broad systemic activation, potentially mitigating the dose-limiting toxicities associated with current IL-2-based therapies.
About Immuno-STAT
Immuno-STAT biologics are designed for targeted modulation of disease-associated T cells in the areas of immuno-oncology and autoimmune disease. Each of our biologic drugs is designed using our proprietary scaffold comprising: 1) a peptide-MHC complex (pMHC) to provide selectivity through interaction with the T cell receptor (TCR), and 2) a unique co-stimulatory signaling molecule to modulate the activity of the target T cells.
The simultaneous engagement of co-regulatory molecules and pMHC binding mimics the signals delivered by antigen presenting cells (APCs) to T cells during a natural immune response. This design enables Immuno-STAT biologics to engage with the T cell population of interest, resulting in highly targeted T cell modulation. Because our drugs are delivered directly in the patient’s body (in vivo), they are fundamentally different from other T cell therapeutic approaches that require the patients’ T cells to be extracted, modified outside the body (ex vivo), and reinfused.