Cue Biopharma, Inc. (CUE) is a clinical-stage biopharmaceutical company leading the charge in the development of a novel class of therapeutic biologics that selectively engage and modulate disease-specific T cells. The company's pioneering Immuno-STAT™ platform has the potential to transform the treatment landscape for both cancer and autoimmune disorders, offering a unique approach to restoring immune balance.
Business Overview and History: Cue Biopharma was founded in 2015 with a mission to harness the power of the immune system by translating nature's cues into targeted protein therapeutics. The company's core technology platform, called Immuno-STAT (Selective Targeting and Alteration of T cells), was licensed from the Albert Einstein College of Medicine. In 2017, Cue Biopharma went public, raising funds to advance its pipeline of oncology and autoimmune drug candidates.
The company's lead oncology program, CUE-101, entered clinical trials for the treatment of human papillomavirus positive head and neck cancer. Around this time, Cue Biopharma also established a collaboration with LG Chem to develop Immuno-STAT candidates in the field of oncology.
Over the next few years, Cue Biopharma encountered some challenges. In 2020, the COVID-19 pandemic caused disruptions to its clinical trial activities. The company also faced setbacks in 2022 when its collaboration partner, Merck, terminated their agreement. Despite these obstacles, Cue Biopharma was able to continue advancing its pipeline, including initiating a clinical trial for its CUE-102 program targeting Wilms Tumor 1 protein.
To bolster its financial position, Cue Biopharma raised additional capital through a public stock offering in 2021 and entered into a loan agreement with Silicon Valley Bank in 2022. The company also expanded its collaborations, signing a deal with Ono Pharmaceutical in 2023 to develop its CUE-401 autoimmune program.
Through strategic partnerships, prudent cash management, and a focus on its core Immuno-STAT technology, Cue Biopharma has navigated the challenges it has faced since its founding in 2015. The company continues to advance its pipeline of novel biologics aimed at selectively modulating the immune system to treat cancer and autoimmune diseases.
Financials and Liquidity: As of June 30, 2024, Cue Biopharma reported cash and cash equivalents of $30.0 million, providing runway into the second quarter of 2025. The company has been disciplined in its capital management, implementing measures to reduce its cash burn from approximately $40 million per year to $30 million per year, primarily through the strategic prioritization of its autoimmune programs and an organizational restructuring.
For the six months ended June 30, 2024, Cue Biopharma reported collaboration revenue of $4.4 million, a significant increase from $1.6 million in the same period of the prior year, driven by revenue recognized from the Ono Pharmaceutical collaboration. Research and development expenses during this period were $19.7 million, compared to $20.0 million in the first half of 2023, reflecting the company's efforts to manage its expenses while advancing its pipeline.
The company's liquidity position is further enhanced by its $80 million at-the-market (ATM) equity offering program, which it has utilized judiciously to raise additional capital without significantly diluting existing shareholders. As of June 30, 2024, Cue Biopharma had sold an aggregate of 9.0 million shares under the ATM program for proceeds of $40.4 million, net of commissions.
Cue Biopharma also has a $10 million term loan facility with First Citizens Bank, which it has utilized to support its operations. As of June 30, 2024, the outstanding principal amount under the term loan was $6.0 million.
For the most recent fiscal year (2023), Cue Biopharma reported revenue of $5.49 million, a net loss of $50.73 million, and operating cash flow of -$39.96 million. In the most recent quarter (Q2 2024), the company reported revenue of $2.66 million, representing a 92.8% increase compared to Q2 2023, primarily due to revenue earned from the Ono Collaboration and Option Agreement. The net loss for Q2 2024 was $10.17 million, with operating cash flow of -$9.99 million.
The company's debt-to-equity ratio stands at 0.43, with a current ratio and quick ratio both at 2.06. As a clinical-stage biopharmaceutical company, Cue Biopharma will need to raise additional capital to fund its future operations and remain a going concern.
Clinical Pipeline and Upcoming Milestones: Cue Biopharma's clinical pipeline is anchored by its CUE-100 series, which has demonstrated impressive results in both oncology and autoimmune disease settings.
In the oncology space, the CUE-101 program for the treatment of recurrent/metastatic HPV-positive head and neck cancer has generated particularly noteworthy data. In the ongoing Phase 1 trial, CUE-101 in combination with the standard-of-care pembrolizumab has achieved an objective response rate of 46%, more than doubling the historical response rate of 19% observed with pembrolizumab alone. Importantly, CUE-101 has also demonstrated a median overall survival (mOS) of 21.8 months in first-line patients, compared to the historical mOS of 12.3 months with pembrolizumab monotherapy.
The CUE-101 monotherapy has shown even more impressive results in the second-line plus setting, with median overall survival of 24.8 months at the 2 mg/kg dose and 20.8 months at the 4 mg/kg dose. This represents a significant improvement over the median OS of 7.5-8.4 months observed with nivolumab and pembrolizumab in the second-line setting.
For patients with low CPS scores (1-19), the combination of CUE-101 and pembrolizumab achieved an objective response rate of 50%, more than triple the historical ORR of approximately 15% with pembrolizumab alone.
The CUE-102 program, targeting the Wilms' Tumor 1 (WT1) antigen, has also shown promising signs of anti-tumor activity in its ongoing Phase 1 trial, with dose-dependent increases in WT1-specific T cell activation and expansion observed in patients across various solid tumor indications, including colorectal, gastric, ovarian, and pancreatic cancer.
On the autoimmune front, the CUE-401 program, being developed in collaboration with Ono Pharmaceutical, has generated preclinical data demonstrating the ability to induce and expand regulatory T cells (Tregs), a key cell type for controlling autoimmune and inflammatory responses. The companies anticipate selecting a lead clinical candidate for CUE-401 and initiating IND-enabling studies in the first half of 2025.
Additionally, the CUE-500 series, led by the CUE-501 program, has shown promise in selectively depleting autoreactive B cells, a potential therapeutic approach for a range of B cell-mediated autoimmune diseases. Cue Biopharma is currently evaluating strategic partnering options to advance the CUE-500 series.
Looking ahead, Cue Biopharma plans to provide updates on the maturing data from its CUE-101 and CUE-102 clinical trials at the upcoming Society for Immunotherapy of Cancer (SITC) conference in November 2024. The company also anticipates reaching several important milestones, including the selection of a lead candidate for CUE-401 and the consummation of a strategic partnership for the CUE-500 series, both expected in the first quarter of 2025.
Risks and Challenges: As a clinical-stage biopharmaceutical company, Cue Biopharma faces the inherent risks associated with the drug development process. The company's success is dependent on its ability to navigate the complex regulatory landscape, successfully complete clinical trials, and ultimately obtain regulatory approvals for its novel Immuno-STAT-based therapeutics.
Additionally, Cue Biopharma operates in a highly competitive landscape, with numerous other companies pursuing similar approaches to modulating the immune system for the treatment of cancer and autoimmune diseases. The company's ability to differentiate its platform and maintain a competitive edge will be crucial to its long-term success.
The company's financial position and liquidity also present potential risks. While Cue Biopharma has implemented measures to extend its runway, it may need to raise additional capital in the future to support its ongoing operations and pipeline development. Failure to secure sufficient funding could hamper the company's ability to execute its strategic initiatives.
Furthermore, Cue Biopharma's reliance on strategic partnerships, such as the collaboration with Ono Pharmaceutical, exposes the company to risks related to the successful execution and maintenance of these agreements. Any disruptions or terminations of these partnerships could have a significant impact on the company's financial and operational performance.
Conclusion: Cue Biopharma is at the forefront of a paradigm shift in the field of immune modulation, leveraging its innovative Immuno-STAT platform to develop a pipeline of targeted biologics that hold the promise of transforming the treatment of both cancer and autoimmune diseases. The company's early clinical successes, particularly with the CUE-101 program in head and neck cancer, have demonstrated the potential of its approach to selectively activate or suppress disease-relevant T cells, offering a compelling alternative to traditional immunotherapies.
The impressive survival data for CUE-101, both as a monotherapy and in combination with pembrolizumab, positions the company favorably to potentially establish a new standard of care in HPV-positive head and neck cancer. The substantial enhancement of survival metrics observed in clinical trials suggests that CUE-101 could become a competitive and clinically meaningful treatment option in this indication.
As Cue Biopharma continues to advance its clinical pipeline and forge strategic partnerships, the company's ability to navigate the regulatory landscape, maintain a competitive edge, and secure sufficient funding will be critical to its long-term success. The company's focus on near-term development milestones in its autoimmune programs, including the advancement of CUE-401 in partnership with Ono Pharmaceutical, demonstrates a strategic approach to pipeline development and resource allocation.
Investors should closely monitor the company's progress, upcoming milestones, and the continued evolution of its Immuno-STAT-based therapeutic candidates. The maturing clinical data from the ongoing CUE-101 and CUE-102 trials, along with potential strategic partnerships for programs like CUE-501, could serve as significant catalysts for the company in the near future.
While Cue Biopharma faces the inherent risks and challenges associated with clinical-stage biopharmaceutical companies, its innovative platform technology and promising clinical results position it as a potential leader in the development of selective immune-modulating therapies. As the company continues to execute its strategy and advance its pipeline, Cue Biopharma's pioneering work could have significant implications for the future of immune-modulating therapies in both oncology and autoimmune diseases.