Cue Biopharma Receives FDA Acceptance of IND Application for CUE-102 in Wilms’ Tumor 1 (WT1) - Expressing Cancers

Cue Biopharma, Inc. recently announced the US FDA has accepted the company’s Investigational New Drug (IND) application for the evaluation of CUE-102, its second interleukin 2 (IL-2)-based CUE-100 series biologic, in a dose escalation and expansion monotherapy Phase 1 trial, which will have a starting dose of 1 mg/kg for the treatment of Wilms’ Tumor 1 (WT1)-positive recurrent/metastatic cancers, with initial focus on gastric, pancreatic, ovarian and colon cancers.

CUE-102 supports the modularity of the IL-2 based CUE-100 series as the core biologic framework is largely conserved with the primary difference being the incorporation of the WT1 T cell epitope. The IND acceptance allowing the dose-escalation trial to begin dosing at 1 mg/kg was supported by the safety and tolerability data from the CUE-101 trial. CUE-101, the first biologic from the CUE-100 series, had a starting dose of 0.06 mg/kg and required approximately 9 months to dose escalate from 0.06 mg/kg to 1 mg/kg. As such, the starting dose of CUE-102 (targeting WT1 expressing cancers) may provide substantive time and cost savings for potentially demonstrating tolerability at therapeutically effective doses.

“The ability to start our dose escalation trial at 1 mg/kg, is significant as it allows us to initiate the trial at a dose level that demonstrated signs of clinical activity in our CUE-101 trial. At this dose level, we can potentially determine tolerability and therapeutically effective doses much more efficiently by truncating the dose escalation process,” stated Ken Pienta, MD, acting Chief Medical Officer of Cue Biopharma. “We believe CUE-102 provides a significant opportunity to address a high unmet medical need in a wide variety of WT1-positive malignancies including colorectal, pancreatic and lung, and potentially offers a tolerable and more effective treatment option to patients in need. We believe CUE-102 has the potential to change the treatment landscape for WT1-positive patients and are very pleased to now begin evaluating its potential benefit in the clinic.”

Anish Suri, PhD, President and Chief Scientific Officer of Cue Biopharma, added “The IND acceptance of CUE-102 is a step forward in support of our strategic vision for pipeline expansion of assets emerging from our IL-2-based CUE-100 series of Immuno-STATs. Since the core framework and the IL-2 components are conserved, the clinical de-risking achieved with CUE-101 should in principle allow us to develop subsequent therapeutic molecules in a significantly expedited and cost-effective manner. To that end, we believe that FDA clearance to initiate the CUE-102 clinical trial at 1 mg/kg dose is an important step forward to the platform de-risking achieved with our current clinical candidate, CUE-101.”

FDA acceptance of the IND application for CUE-102 is another important milestone for Cue Biopharma in their multi-target strategic collaboration with LG Chem Life Sciences, the life sciences division of LG Chem Ltd., to develop multiple Immuno-STAT biologics focused in the field of oncology.

Leveraging the Immuno-STAT (Selective Targeting and Alteration of T cells) platform of targeted interleukin 2 (IL-2) therapies and the ongoing development of CUE-101, CUE-102 is being developed as a novel therapeutic fusion protein to selectively activate tumor antigen-specific T cells to treat Wilms’ Tumor 1 (WT1)-expressing cancers. CUE-102 consists of two human leukocyte antigen (HLA) molecules presenting a WT1 peptide, four affinity-attenuated IL-2 molecules, and an effector attenuated human immunoglobulin G (IgG1) Fc domain. WT1 is a well-recognized onco-fetal protein known to be over-expressed in a number of cancers, including solid tumors and hematologic malignancies.

The CUE-100 series consists of Fc-fusion biologics that incorporate peptide-major histocompatibility complex (pMHC) molecules along with rationally engineered interleukin 2 (IL-2) molecules. These singular biologics are anticipated to selectively target, activate and expand a robust repertoire of tumor-specific T cells directly in the patient’s body. 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.

The company’s Immuno-STAT (Selective Targeting and Alteration of T cells) platform 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-major histocompatibility 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 selective T cell modulation. Because our drug candidates 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.

LG Chem Life Sciences is a business division within LG Chem, engaged in the development, manufacturing, as well as commercializing pharmaceutical products globally. LG Chem Life Sciences seeks to expand and make global presence by focusing on key core therapeutic areas of Immunology, Oncology, and Metabolic Diseases (specifically, diabetes and related metabolic diseases). To achieve such, its strategy is to actively pursue global collaboration encompassing from asset-centric to strategic investment and collaboration. For more information, visit innovation.lgchem.com.

Cue Biopharma, a clinical-stage biopharmaceutical company, is developing a novel class of injectable biologics to selectively engage and modulate targeted T cells within the patient’s body to transform the treatment of cancer, infectious disease and autoimmune disease. The company’s proprietary platform, Immuno-STAT (Selective Targeting and Alteration of T cells) is designed to harness the body’s intrinsic immune system without the need for ex vivo manipulation.

Headquartered in Boston, MA, we are led by an experienced management team and independent Board of Directors with deep expertise in immunology and immuno-oncology as well as the design and clinical development of protein biologics. For more information, visit www.cuebiopharma.com.