IN8bio, Inc. (NASDAQ:INAB) is a clinical-stage biopharmaceutical company at the forefront of developing novel gamma-delta (γδ) T cell-based immunotherapies for cancer patients. The company's innovative approach leverages the unique properties of γδ T cells to effectively target and eliminate malignant cells, positioning IN8bio as a leader in the field of cellular immunotherapy.
Company Background
Founded in 2015 as Incysus, Inc. in Delaware, the company underwent several corporate transformations before becoming IN8bio, Inc. in August 2020. The company's origins trace back to technology licensed from the University of Alabama at Birmingham Research Foundation, Emory University, and Children's Healthcare of Atlanta, Inc., focusing on the use of gamma-delta T cells for immunotherapy applications in cancer treatment.
IN8bio's proprietary DeltEx platform, developed from this licensed technology, has been the cornerstone of its research and development efforts. The company's early years were dedicated to research and preclinical development, with its first clinical trial for INB-200 in glioblastoma initiated in 2019. This was followed by the advancement of INB-100 for acute myeloid leukemia into clinical development through an investigator-sponsored trial.
The company's journey has not been without challenges. In 2024, IN8bio implemented a strategic restructuring, suspending enrollment in the INB-400 Phase 2 clinical trial for glioblastoma and narrowing its focus to the INB-100 program for acute myeloid leukemia. This decision was driven by the difficult financing environment and lack of investor interest in the glioblastoma program. The restructuring also included a significant workforce reduction of 49% to preserve cash resources and focus on advancing the INB-100 program.
IN8bio's Pipeline and Clinical Developments
The cornerstone of IN8bio's pipeline is INB-100, an allogeneic gamma-delta T cell therapy designed for the treatment of high-risk leukemias, including acute myeloid leukemia (AML). The Phase 1 trial of INB-100 has demonstrated impressive results, with 100% of evaluable AML patients (n=10) remaining alive, progression-free, and in durable complete remission through one year as of May 31, 2024. Furthermore, as of August 30, 2024, 100% of AML patients remain relapse-free after a median follow-up of 18.7 months.
Notably, the gamma-delta T cells used in the INB-100 product have exhibited long-term persistence and in vivo expansion, a first for any donor-derived, allogeneic cellular therapy. These findings underscore the potential of INB-100 to significantly improve outcomes for high-risk leukemia patients, a population with limited treatment options and poor prognosis.
Building on the success of INB-100, IN8bio has received regulatory guidance from the FDA to advance the program towards a registrational trial, with relapse-free survival as the primary endpoint. The company is currently expanding the INB-100 trial to enroll up to approximately 25 patients at the recommended Phase 2 dose, while also exploring the addition of a parallel observational cohort as a control. IN8bio plans to complete the additional enrollment in the expansion cohort at the recommended Phase 2 dose in 2025, with long-term follow-up results anticipated in late 2025 and 2026.
In addition to the INB-100 program, IN8bio has demonstrated the versatility of its DeltEx platform through the development of other product candidates. INB-200, an autologous gamma-delta T cell therapy, is being evaluated in an investigator-sponsored Phase 1 trial for the treatment of newly diagnosed glioblastoma (GBM). Preliminary data from this trial presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting showed that 92% of evaluable patients exceeded the median progression-free survival (PFS) of 7 months typically achieved with standard-of-care therapy.
Unfortunately, in September 2024, IN8bio announced the suspension of patient enrollment in the INB-400 Phase 2 trial for newly diagnosed GBM, citing the difficult financing environment and investor lack of interest in pursuing the GBM program. The company will continue to monitor patients previously enrolled in the INB-400 and INB-200 trials while exploring strategic alternatives for the GBM program.
IN8bio's preclinical pipeline includes INB-300, which focuses on targeting various solid and liquid tumors using a dedicated non-signaling gamma-delta T cell-based chimeric antigen receptor (nsCAR) construct. The company presented additional preclinical data demonstrating proof-of-concept in vitro studies against leukemia antigen targets CD33 and CD123 at the American Association for Cancer Research Annual Meeting in 2024.
Financials and Liquidity
IN8bio's financial performance has been consistent with the early-stage nature of its clinical development programs. For the fiscal year ended December 31, 2023, the company reported no revenue and a net loss of $30.0 million, primarily driven by research and development expenses of $16.8 million and general and administrative expenses of $13.5 million.
For the nine months ended September 30, 2024, IN8bio reported a net loss of $24.3 million, compared to $22.4 million for the same period in 2023. Research and development expenses for this period were $13.4 million, up from $12.3 million in the previous year, reflecting the progress of its clinical programs. General and administrative expenses decreased slightly to $10.0 million from $10.4 million in the prior year period.
As of September 30, 2024, IN8bio had cash and cash equivalents of $4.0 million. However, in October 2024, the company closed a $12.4 million private placement, resulting in net proceeds of $11.6 million. This additional capital infusion is expected to fund the company's current operating plan into December 2025. The decision to suspend the INB-400 program and reduce its workforce by approximately 49% is expected to further strengthen IN8bio's financial position and enable it to focus its resources on the continued development of the INB-100 program.
It is worth noting that IN8bio's auditor included a "going concern" emphasis in its report for the fiscal year ended December 31, 2023, citing the company's recurring losses and negative cash flows from operations. This highlights the need for IN8bio to secure additional funding or achieve meaningful milestones to ensure its long-term viability.
The company's financial metrics as of the most recent reporting period include:
- Debt/Equity Ratio: 0.64 - Current Ratio: 1.84 - Quick Ratio: 1.84 - Annual Operating Cash Flow: -$23.3 million - Annual Free Cash Flow: -$23.9 million
These metrics underscore the company's need for additional capital to support its ongoing operations and clinical development programs.
Competitive Landscape and Risks
The field of cellular immunotherapy, particularly gamma-delta T cell-based therapies, is an emerging and competitive landscape. IN8bio faces competition from other companies developing similar approaches, such as Iovance Biotherapeutics, Adicet Bio, and Kuur Therapeutics, among others.
Additionally, as a clinical-stage company, IN8bio is subject to the inherent risks associated with the development and commercialization of novel therapies. These include the potential for delays or failures in clinical trials, regulatory hurdles, manufacturing challenges, and the ability to secure adequate funding to support its operations and future growth.
Furthermore, the company's heavy reliance on the success of its lead candidate, INB-100, poses a significant risk. Any setbacks or unfavorable outcomes in the ongoing or future clinical trials of INB-100 could have a material adverse impact on IN8bio's business and prospects.
Outlook and Conclusion
IN8bio's unwavering focus on advancing its gamma-delta T cell-based therapies, particularly the INB-100 program, positions the company as a frontrunner in the field of cellular immunotherapy. The impressive results observed in the INB-100 Phase 1 trial, with 100% of AML patients remaining relapse-free, underscore the potential of this approach to transform the treatment landscape for high-risk leukemia patients.
As IN8bio continues to expand the INB-100 trial and seeks regulatory guidance for a potential registrational study, the company's ability to maintain its momentum and secure additional funding will be crucial. The recent $11.6 million net proceeds from a private placement provide a critical financial lifeline, allowing IN8bio to concentrate its resources on the most promising aspects of its pipeline.
However, the challenges inherent in the biopharmaceutical industry, including the competitive landscape and the inherent risks of clinical development, remain ever-present. Investors in IN8bio must carefully weigh the potential upside of the company's innovative gamma-delta T cell therapies against the uncertainties and risks that come with an early-stage biotechnology company.
Overall, IN8bio's unwavering dedication to advancing its gamma-delta T cell platform and the promising data from its lead program, INB-100, make it a compelling story in the rapidly evolving field of cancer immunotherapy. As the company navigates the next stages of clinical development and strategic decision-making, investors will closely monitor its ability to capitalize on the unique advantages of its technology and deliver meaningful outcomes for patients in need.