IN8bio Announces New Preclinical Data for Gamma-Delta nsCAR-T Cell Therapy Platform at AACR 2024
- Promising preclinical data on IN8bio's nsCAR platform, INB-300, demonstrated improved selectivity in targeting leukemia cells while preserving healthy tissue.
- The technology aims to prevent off-target effects common in CAR-T therapies, potentially expanding treatment options for myeloid malignancies and solid tumors.
- Results presented at AACR 2024 revealed enhanced tumor killing capabilities without significant harm to healthy cells, indicating a 5.5x increase in selectivity.
- IN8bio plans to optimize the platform further for safer and more effective cancer treatments.
- None.
Insights
The recent findings from IN8bio regarding their non-signaling gamma-delta T cell based Chimeric Antigen Receptor-T cell (nsCAR) platform, specifically INB-300, signify a promising advancement in cancer immunotherapy. Gamma-delta T cells are a subset of T cells that possess innate-like properties, enabling them to recognize and eliminate cancerous cells while sparing healthy cells. This inherent property is leveraged in IN8bio's nsCAR technology to potentially address one of the significant limitations of current CAR-T therapies: the on-target off-tumor toxicity.
The ability of INB-300 to selectively target leukemia cells and not healthy tissue could be a game-changer, especially for conditions like acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), where traditional treatments have been less effective. The data suggesting a 1.8x increase in tumor killing capability without significant damage to healthy cells could translate into a more effective and safer treatment option for patients. This could lead to a wider therapeutic window, meaning higher doses could be administered with potentially fewer side effects.
However, it's important to note that these are preclinical findings and the real test will be how these results translate into human clinical trials. The safety profile, as well as the efficacy demonstrated in a controlled environment, will be critical to the success of INB-300 as it progresses towards Investigational New Drug (IND) enabling studies.
IN8bio's preclinical data on their nsCAR platform has significant implications for the field of adoptive cell therapies. The integration of membrane-bound IL-15 co-expression could potentially enhance not only the efficacy but also the persistence and overall survival of these modified T cells within the patient's body. IL-15 is known for its role in the survival and proliferation of T cells and its membrane-bound form may provide a more localized and sustained stimulation to the nsCAR T cells.
What stands out is the reported average 5.5x increase in selectivity, which is a measure of the technology's ability to discriminate between cancerous and healthy cells. This high degree of selectivity could lead to a reduction in the adverse events commonly associated with CAR-T therapies, such as cytokine release syndrome (CRS) and neurotoxicity, which are often the result of indiscriminate T cell activation.
From a research perspective, the proprietary constructs targeting CD33 and/or CD123 are also noteworthy. These antigens are commonly overexpressed in myeloid leukemias, making them ideal targets for such therapies. The nsCAR's ability to target these antigens without the signaling domain that typically leads to T cell activation upon antigen recognition could be the key to reducing the aforementioned toxicities.
The biotechnology sector is highly driven by innovation and IN8bio's new preclinical data could have significant financial implications if the therapy proves successful in later stages of development. The nsCAR platform's potential to mitigate on-target off-tumor toxicity could position IN8bio favorably in the competitive landscape of CAR-T therapies, especially for treating myeloid malignancies and solid tumors, which have been challenging targets for existing therapies.
Investors should consider the long development timelines and the capital required to bring such therapies from preclinical to commercial stages. While the preclinical results are promising, the transition to clinical efficacy, regulatory approval and market acceptance is fraught with risk. However, the unique approach of IN8bio in enhancing the selectivity and safety profile of CAR-T therapies could attract partnership opportunities, licensing deals, or even acquisition interest from larger pharmaceutical companies seeking to bolster their oncology pipelines.
It's also worth noting that the market for CAR-T therapies is rapidly growing, with increasing incidence rates of hematologic cancers and a growing demand for innovative treatments. A successful nsCAR therapy could capture a significant market share and provide substantial returns on investment. Nonetheless, the biotech sector's volatility and the high risk associated with drug development should be carefully weighed by stakeholders.
- Preclinical data supports potential for proprietary nsCAR platform to selectively eliminate cancer cells while preserving healthy tissue
- Gamma-delta nsCAR platform emerging as an advanced technology for targeting hematologic and solid tumor cancers
NEW YORK, April 09, 2024 (GLOBE NEWSWIRE) -- IN8bio, Inc. (Nasdaq: INAB) a clinical-stage biopharmaceutical company developing innovative gamma-delta T cell therapies, today announced new preclinical data from its non-signaling gamma-delta T cell based Chimeric Antigen Receptor-T cell (nsCAR) platform, known as INB-300, that demonstrated improved selectivity to target leukemia cells while preserving healthy ones. The data support the potential for nsCAR to have a wider therapeutic window and to be used to prevent on-target off-tumor killing of healthy tissue that may express the CAR-T target. The data was presented in a poster session at the American Association for Cancer Research (AACR) Annual Meeting 2024 on April 9, 2024.
IN8bio's nsCAR platform is based on the natural ability of gamma-delta T cells to distinguish between healthy and malignant tissue. By using a Chimeric Antigen Receptor (CAR) that lacks a signaling domain, IN8bio believes it has created a technology that enables these cells to differentiate between tumor and healthy tissue, even when both express the CAR-targeted antigen.
Approved CAR-T therapies have shown remarkable efficacy against B cell malignancies, offering hope to patients with limited treatment options. However, extending this therapy to myeloid malignancies and solid tumors has proven challenging since the antigens they target are also often found on the surface of healthy blood cells and tissues. This unintended targeting of healthy cells and tissues has led to many of the toxicities, including patient deaths, observed in prior CAR-T therapies and has limited their utility. Unlike traditional CAR-T therapy, IN8Bio’s nsCAR is designed to direct the gamma delta T cell to its target while maintaining their unique gamma-delta T cell receptors, allowing them to identify and specifically eliminate heterogeneous tumor cells through recognition of tumor-associated stress antigens.
The new data presented at AACR included results from proprietary constructs targeting CD33 and/or CD123 for in vitro evaluation against various types of leukemia, including acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). The study results demonstrated notable differences between cells expressing traditional signaling CARs and those expressing the nsCAR constructs, which include a reduction in activation-induced cell death with nsCAR constructs.
The nsIL3-33mb15 CAR (CD123+CD33+IL-15) enhancement of the gamma delta T cells against leukemia cells demonstrated an average 1.8x increase in tumor killing capability across three AML cell lines (HL-60, KG-1a and MOLM-13), compared to unmodified gamma-delta T cells as measured by a 24-hour cytotoxicity assay. Importantly, the nsCAR cells did not lead to significant killing of healthy cells expressing the CD33 or CD123 target, demonstrating the selectivity of the nsCAR platform. Results were run in triplicate and on average the selectivity was increased by 5.5x. Across all runs, killing by the nsIL3-33mb15 construct against healthy CD34+ HPCs was below that of un-transduced control gamma-delta T cells.
“INB-300 can selectively target leukemia cells while preserving healthy tissue. We are now conducting further optimization to improve the integration of membrane-bound IL-15 co-expression to potentially enhance both the efficacy and safety of next-generation adoptive cell therapies against a wider spectrum of cancers,” said Lawrence Lamb, Ph.D., co-founder and Chief Scientific Officer of IN8bio. “These results can potentially improve INB-300, as we advance towards IND enabling studies of our next-generation gamma-delta T cell therapies to treat cancers.”
About INB-300
INB-300 is an nsCAR gamma-delta T cell platform with several preclinical product candidates, including the INB-330 program against AML targets, that combine our expertise in gamma-delta T cells and genetic engineering. These nsCAR constructs lack signaling domains in order to take advantage of the unique properties of gamma-delta T cells to differentiate between healthy and tumor tissues. IN8bio is advancing new nsCAR constructs against multiple targets to treat both solid and liquid tumors.
About IN8bio
IN8bio is a clinical-stage biopharmaceutical company developing gamma-delta T cell-based immunotherapies for cancer patients. Gamma-delta T cells are a specialized population of T cells that possess unique properties, including the ability to differentiate between healthy and diseased tissue. The company’s lead program, INB-400, is in a Phase 2 trial in glioblastoma multiforme (GBM). Additional programs include Phase 1 trials in solid and hematologic tumors, including INB-200 for GBM and INB-100 for patients with hematologic malignancies undergoing transplantation. For more information about IN8bio, visit www.IN8bio.com.
Forward-Looking Statements
This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding the ability of IN8bio’s nsCAR platform to (i) selectively target and eradicate cancer cells while preserving healthy tissue through recognition of tumor-associated stress antigens and (ii) have a wider therapeutic window and to be used to prevent on-target off-tumor killing of healthy tissue that may express the CAR-T target; IN8bio’s ability to enhance both the efficacy and safety of next-generation adoptive cell therapies against a wider spectrum of cancers; and IN8bio’s ability to advance its pipeline of novel gamma-delta CAR-T therapies to treat additional cancers, including both solid and liquid tumors. IN8bio may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions, and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of IN8bio’s product candidates, including patient enrollment and follow-up and IN8bio’s ability to meet anticipated deadlines and milestones; the risk that IN8bio may not realize the intended benefits of its DeltEx platform; availability and timing of results from preclinical studies and clinical trials; whether the outcomes of preclinical studies will be predictive of clinical trial results; whether initial or interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; the risk that trials and studies may be delayed and may not have satisfactory outcomes; potential adverse effects arising from the testing or use of IN8bio’s product candidates; uncertainties related to regulatory approvals to conduct trials or to market products; IN8bio’s reliance on third parties, including licensors and clinical research organizations; and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, that are described in greater detail in the section entitled “Risk Factors” in our Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on March 14, 2024, as well as in other filings IN8bio may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and IN8bio expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances, or otherwise, except as otherwise required by law.
Corporate Contact:
IN8bio, Inc.
Glenn Schulman, PharmD, MPH
203.494.7411
gdschulman@IN8bio.com
Investors
Meru Advisors
Lee M. Stern
lstern@meruadvisors.com
Media Contact
Kimberly Ha
KKH Advisors
917.291.5744
kimberly.ha@kkhadvisors.com
FAQ
What is the name of the company mentioned in the press release?
What is the technology platform discussed in the press release?
What event featured the presentation of the new preclinical data?
What is the goal of IN8bio's nsCAR platform?
What were the key findings of the study presented at AACR 2024?
