Cue Biopharma, Inc.

The company, Cue Biopharma, Inc., is a clinical-stage biopharmaceutical entity focused on developing injectable therapeutics designed to selectively engage and modulate disease-specific T cells for autoimmune and inflammatory diseases, leveraging its Immuno-STAT® platform ¹. The core business model involves generating revenue through collaboration and license agreements, as well as potential future product sales, though the company has no history of commercial revenue from product sales ². Primary customer segments are not explicitly detailed, but the company's focus on autoimmune and inflammatory diseases implies targeting patients suffering from these conditions.

The company's product pipeline is categorized into three series. The CUE-400 series targets autoimmune diseases by exploiting TGF-β and IL-2 signaling to induce an anti-inflammatory process, foster regulatory T cell (Treg) proliferation, and induce Tregs from T effector cells, with CUE-401 being the lead preclinical candidate ³. The CUE-500 series, including CUE-501, is designed for targeted anti-viral T cell-mediated depletion of pathogenic cells, such as autoreactive B cells, for autoimmune conditions ⁴. The CUE-100 series, which historically focused on oncology with CUE-101 for HPV+ cancers and CUE-102 for WT1-expressing cancers, aims to selectively activate and expand tumor-specific T cells ⁵.

For the fiscal year ended December 31, 2025, the company reported total research and development expenses of $37.7 million ⁶, compared to $36.3 million ⁷ for the year ended December 31, 2024. Employee compensation for research and development was $10.3 million ⁸ in 2025, down from $13.1 million ⁹ in 2024. Contract manufacturing costs increased to $8.8 million ¹⁰ in 2025 from $5.4 million ¹¹ in 2024. Facilities and overhead costs were $4.9 million ¹² in 2025, a slight decrease from $5.1 million ¹³ in 2024. Lab costs decreased to $3.9 million ¹⁴ in 2025 from $4.9 million ¹⁵ in 2024. Acquired in-process research and development costs were $3.9 million ¹⁶ in 2025, with no comparable figure in 2024. Clinical trial costs decreased to $3.7 million ¹⁷ in 2025 from $7.1 million ¹⁸ in 2024. License fees increased to $1.6 million ¹⁹ in 2025 from $0.1 million ²⁰ in 2024. Professional fees remained consistent at $0.6 million ²¹ for both years. The company had cash and cash equivalents of $27.1 million ²² as of December 31, 2025, and an accumulated deficit of $368.5 million ²³.

Year-over-year comparisons show a slight increase in total research and development expenses from $36.3 million ⁷ in 2024 to $37.7 million ⁶ in 2025. This was driven by increases in contract manufacturing costs and acquired in-process research and development costs, offset by decreases in employee compensation, lab costs, and clinical trial costs. License fees also saw a significant increase. The company's cash and cash equivalents decreased, and the accumulated deficit continued to grow, reflecting ongoing operating losses.

Significant operational developments during the period include the regaining of worldwide development and commercialization rights for CUE-401 from Ono Pharmaceutical, effective March 6, 2025 ²⁴. On April 10, 2025, the company entered into a Collaboration and License Agreement with Boehringer Ingelheim International GmbH (BI) for the research, development, and commercialization of B cell depletion molecules, including CUE-501 ²⁵. In connection with this, the company paid Einstein $0.9 million ²⁶ in fees related to an amendment to the Einstein License. On November 6, 2025, ImmunoScape Pte. Ltd. (IMSCP) exercised its option to obtain licenses for the CUE-100 series, including CUE-101 and CUE-102, for oncology indications ²⁷. In connection with the IMSCP agreement, the company received an aggregate of $9.5 million ²⁸, net of withholding taxes, in the fourth quarter of 2025 and is entitled to receive an additional $5.0 million ²⁹ before the first anniversary of the effective date. The company also regained rights to the LG Chem Territory for the CUE-101 program on March 11, 2025 ³⁰.

The company anticipates receiving human safety data for CUE-401 starting in the second half of 2026 ³¹, following the planned filing of an Investigational New Drug (IND) application in the second quarter of 2026 ³². These early clinical trial results are expected to provide pharmacokinetic and pharmacodynamic evidence to support the premise of establishing immune balance and inducing durable immune tolerance with CUE-401, which the company believes could represent a breakthrough as a new standard of care in multiple high-value autoimmune disease indications.

A major growth area for the company is the development of CUE-401 for autoimmune diseases. This preclinical, bifunctional fusion protein is designed to promote immune tolerance by inducing newly formed regulatory T cells (iTregs) from T effector cells and expanding existing natural regulatory T cells (nTregs), while reducing pro-inflammatory autoreactive cells ³. The company believes this approach has the therapeutic potential to re-establish immune balance and induce tolerance across a range of T cell-mediated autoimmune and inflammatory diseases, offering long-lasting tolerance ³. Scale-up manufacturing and other IND-enabling studies for CUE-401 are nearing completion, with GLP toxicology studies already finished in both mice and non-human primate species ³. The Phase 1 trial for CUE-401 will be a two-part study, comprising a single ascending dose and a multiple ascending dose in healthy volunteers ³.

Another growth vector is the CUE-500 series, which has been licensed to Boehringer Ingelheim International GmbH (BI) for research, development, and commercialization ²⁵. This series is designed to enable targeted anti-viral T cell-mediated depletion of pathogenic cell types, including autoreactive B cells, for autoimmune diseases ⁴. The company believes this novel approach, by redirecting existing anti-viral memory T cells, offers highly effective killing of targeted cells while potentially reducing side effects compared to competing approaches ⁴. The modularity of the CUE-500 series suggests therapeutic potential across multiple disease areas by swapping different cell-targeting antibody domains ⁴.

The company expects research and development expenses to remain consistent in future periods ³³. The company's current operating plans indicate sufficient funds to meet obligations into the first quarter of 2027 ³⁴. The company plans to finance future cash needs through a combination of equity offerings, collaborations, and other strategic alliances ³⁵.

The company has flagged several structural headwinds and execution risks. Volatility in capital markets and general economic conditions, including heightened inflation, interest rate and currency rate fluctuations, trade barriers, and geopolitical events, may hinder the ability to raise required funds ³⁵. The company's reliance on third-party CROs and CMOs for clinical trials and manufacturing introduces risks of delays, non-compliance, or termination of agreements ³⁶. Changes in U.S. and international trade policies, such as tariffs and export rules, could negatively impact costs of materials, production processes, and supply chain stability ³⁷. Specifically, the BIOSECURE Act and potential blacklisting of Chinese biotechnology companies could disrupt reliance on CMOs and service providers in China ³⁸. The company is also subject to the Inflation Reduction Act (IRA), which requires manufacturers of certain drugs to engage in price negotiations with Medicare, potentially capping prices and subjecting manufacturers to civil monetary penalties or excise taxes for non-compliance ³⁹. The IRA also established inflation rebate programs under Medicare Part B and Part D ⁴⁰.

The company faces material risks including recurring losses from operations that raise substantial doubt about its ability to continue as a going concern, with cash and cash equivalents of $27.1 million ²² as of December 31, 2025, projected to last only into the first quarter of 2027 ³⁴. Significant competition from established and emerging pharmaceutical and biotechnology companies, many with greater financial and technical resources, poses a risk to the commercial success of its drug product candidates ⁴¹. Regulatory risks are substantial, as the marketing approval process is expensive, time-consuming, and uncertain, with potential for delays or denial of approval, and ongoing post-approval regulatory requirements ⁴². Changes in U.S. and international trade policies, including tariffs and export restrictions, could negatively impact costs and supply chains, as exemplified by the BIOSECURE Act and potential investigations into Chinese biotechnology companies ³⁷. The Inflation Reduction Act (IRA) introduces risks related to Medicare price negotiations and inflation rebates, potentially capping prices and imposing penalties ³⁹. Furthermore, the company is exposed to product liability lawsuits, intellectual property infringement claims, and the risk of misconduct by employees or partners, which could lead to substantial liabilities, fines, or reputational harm ⁴³.

Management's message to shareholders emphasizes leveraging the differentiated Immuno-STAT platform to establish new standards of care, forge strategic partnerships, and accelerate clinical development. The company intends to maximize shareholder value by focusing on the development of CUE-401, for which an IND application is being prepared for filing in the second quarter of 2026 ³², with human safety data anticipated in the second half of 2026 ³¹. Strategic priorities include advancing CUE-401 through clinical development, as well as maintaining and establishing collaborations, such as the agreements with BI for CUE-501 and IMSCP for the CUE-100 series. Management acknowledges the need for substantial additional financing to support future operations and growth, expecting to fund these needs through equity offerings, collaborations, and other strategic alliances ³⁵.