IN8bio Announces Advanced Gamma-Delta (γδ) T cell Engager (TCE) Platform for Oncology and Autoimmune Diseases

Rhea-AI Summary

IN8bio (NASDAQ: INAB) has unveiled INB-600, a novel gamma-delta (γδ) T cell-based TCE platform designed to overcome the limitations of current γδ TCEs. The platform's first candidate, INB-619, targets CD19 for applications in leukemias, lymphomas, and autoimmune diseases.

Key preclinical findings for INB-619 include:

• Rapid B-cell depletion with γδ T cells expanding up to 450-fold
• Simultaneous activation of both Vδ1+ and Vδ2+ T cell subsets
• Lower IL-6 secretion, potentially reducing risks of cytokine release syndrome (CRS) and neurotoxicity (ICANs)

The platform represents the first known approach capable of sustained γδ T cell expansion, offering potentially greater safety and tolerability compared to current CAR-T and TCE approaches. IN8bio plans to evaluate INB-619 in preclinical studies and seek partners for future IND-enabling trials.

Positive

• First-in-class platform enabling sustained γδ T cell expansion up to 450-fold
• Demonstrated rapid B-cell depletion in preclinical models
• Lower risk of severe side effects (CRS and ICANs) due to reduced IL-6 secretion
• Potential applications in both oncology and autoimmune diseases

Negative

• Still in early preclinical stage
• Requires partnership for IND-enabling trials advancement
• No clinical validation of safety and efficacy claims yet

Insights

Oncology Research Expert

IN8bio's announcement of their γδ T cell Engager (TCE) platform represents a significant technological advancement in the immuno-oncology field. The key innovation addresses a fundamental limitation of existing γδ TCEs – insufficient effector cells to drive meaningful clinical impact. Their approach enables 450-fold expansion of γδ T cells while maintaining their cytotoxic activity.

What's particularly noteworthy is the platform's ability to simultaneously activate and expand both Vδ1+ and Vδ2+ T cell subsets. This dual-targeting approach leverages complementary properties: Vδ2+ cells' rapid antigen presentation and Vδ1+ cells' resistance to exhaustion and tissue-resident properties. The combined effect potentially creates deeper and more sustained B-cell depletion than current approaches.

The reduced IL-6 secretion profile addresses one of the most significant barriers to broader adoption of cell therapies – cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANs). These toxicities have CAR-T therapy expansion into autoimmune indications despite their efficacy.

While still in preclinical stages with their lead candidate INB-619 targeting CD19, the platform's design principles could enable applications across multiple oncology and autoimmune indications. The company's strategy to seek partnerships for IND-enabling studies suggests they recognize the substantial resources required to advance multiple candidates through clinical development.

Biotechnology Investment Analyst

This announcement positions IN8bio in the highly competitive bispecific antibody and cell therapy market with a differentiated approach that could expand their addressable market beyond oncology into autoimmune diseases. The company's market capitalization of just $18.4 million appears disproportionately small relative to the potential of this platform technology if it successfully translates to human clinical settings.

The CD19-targeted space is crowded but lucrative, with approved CAR-T therapies commanding premium pricing. However, their complex manufacturing, lymphodepletion requirements, and safety concerns have market penetration. IN8bio's approach potentially addresses these limitations, which could drive significant value if validated clinically.

Investors should note the company is still seeking partners for IND-enabling studies, indicating substantial capital requirements before clinical validation. This suggests near-term dilution risk as the company funds continued development. The focus on partnership also indicates the company recognizes the challenges of independently commercializing complex biologics.

The emphasis on both oncology and autoimmune applications is strategically sound, as the autoimmune market represents a substantial expansion opportunity. Major players like Roche, AbbVie, and Novartis have been aggressively pursuing safer B-cell depletion technologies, which could position IN8bio as an attractive acquisition target if preclinical data translates to humans.

While promising, the technology remains unproven in clinical settings. The platform's initial validation could represent a meaningful catalyst for INAB shares if the safety advantages are maintained in eventual human studies.

• Proprietary platform represents the first known approach capable of sustained γδ T cell expansion, eliminating target cells with robust potency
• INB-619, a next generation γδ TCE targeting CD19, eradicates B cells in preclinical models, maintaining depletion over time as γδ T cells expand in response to TCE stimulation
• γδ TCE targets and expands both Vδ1+ and Vδ2+ T cells, potentially leading to longer lasting immune responses and deeper B cell depletion
• Unlike traditional TCEs and CAR-T therapies, γδ T cells naturally secrete lower levels of IL-6, potentially reducing the risk of cytokine release syndrome (CRS) and neurotoxicity (ICANs)
• Access the webcast discussing the novel γδ TCE platform today at 10:30 a.m. ET during the TD Cowen 45^th Annual Health Care Conference
  

NEW YORK, March 03, 2025 (GLOBE NEWSWIRE) -- IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company developing innovative gamma-delta (γδ) T cell therapies, today unveiled INB-600, its potentially breakthrough next generation γδ T cell-based TCE platform. It is designed to address one of the biggest shortcomings of current existing γδ TCEs – insufficient numbers of γδ T cell effector cells to drive real clinical impact. This groundbreaking platform leverages γδ T cells’ unique properties targeting applications in both oncology and autoimmune indications with potentially greater safety and tolerability than current CAR-T and TCE approaches.

The platform’s first candidate, INB-619, targets CD19, a key marker broadly found on B cells, which play a central role in leukemias, lymphomas, and autoimmune diseases. In preclinical models, INB-619 demonstrated:

• Rapid and sustained B-cell depletion – target cells were eradicated as γδ T cells continued expanding up to 450-fold with continued proliferation until the target cells were undetectable.
• Simultaneous expansion and activation of both major γδ T cell subsets (Vδ1+ and Vδ2+) leverages both the rapid antigen presenting properties of Vδ2+ T cells and the longer-term resistance against exhaustion and tissue residence properties of Vδ1+ T cells, potentially resulting in deeper B cell depletion.
• Lower cytokine (IL-6) secretion, potentially reducing the risk of dangerous side effects such as CRS and ICANs, two of the most severe side effects limiting CAR-T and traditional CD3-TCE adoption in autoimmune indications.
  

William Ho, Chief Executive Officer and co-founder of IN8bio, commented, “As the industry rapidly chased immunology and inflammation (I&I) indications, we saw a major unmet need for a therapy that provides deep B cell depletion, ease of delivery with no required lymphodepletion, and improved overall safety and tolerability. Most γδ TCEs have failed because they can’t engage the limited number of effector cells to eliminate their targets. Our INB-600 platform is working to change the equation by not only targeting B cells, but also by actively expanding the γδ T cell immune army needed for deep, lasting B cell depletion. By leveraging our expertise in γδ T cell biology, we have worked to develop a breakthrough technology that combines exceptional preclinical potency, while broadly expanding immune surveillance and potentially avoiding the dangerous side effects of existing approaches. We believe this platform could have significant applications across oncology as well as autoimmune diseases.”

TCEs are a class of bispecific antibody therapies that work by binding both a target cell and a T cell, bringing them into close proximity so the T cell can efficiently attack and destroy its target. Traditional TCEs, such as those targeting CD3 – have demonstrated strong target killing abilities but often have severe limitations, including the potential to drive T cells to exhaustion and induce severe toxicities such as CRS and ICANs. γδ T cells naturally secrete lower levels of inflammatory cytokines such as IL-6, which suggests substantially less risk of CRS, which may translate to improved safety and tolerability in future clinical applications. Notably, to date, IN8bio has not observed any CRS or neurotoxicities in any of its on-going γδ T cell clinical programs.

IN8bio plans to evaluate INB-619 in preclinical studies and seek potential partners to support future IND-enabling trials. We remain focused on to pushing the boundaries of next generation γδ cell-based immunotherapies as it pursues its mission of Cancer Zero_™ - a future where cancer is fully eliminated.

Webcast details
TD Cowen 45^th Annual Health Care Conference
Date/Time: Monday, March 3, 2025, at 10:30 a.m. ET.
Webcast link: https://wsw.com/webcast/cowen177/inab/1991262

A live webcast and replay will also be available under "Events and Presentations" in the News & Presentations section of the IN8bio website at https://investors.in8bio.com.

About IN8bio
IN8bio is a clinical-stage biopharmaceutical company developing gamma-delta (γδ) 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-100, is focused on AML evaluating haplo-matched allogeneic γδ T cells given to patients following a hematopoietic stem cell transplant. The Company is also evaluating autologous DeltEx DRI γδ T cells, in combination with standard of care, for glioblastoma. 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 INB-619 to (i) eradicate B cells and maintain depletion over time; (ii) lead to longer-lasting immune responses and deeper B cell depletion and (iii) reduce the risk of dangerous side effects such as CRS and ICANs; the ability of the INB-600 platform to (x) address the issue of insufficient numbers of γδ T cell effector cells to drive real clinical impact and (y) have significant applications across oncology as well as autoimmune diseases; IN8bio’s ability to seek potential partners to support future IND-enabling trials; and IN8bio’s ability to achieve anticipated milestones, including expected presentations and data readouts from its trials, enrollment of additional patients in its clinical trials, and advancement of clinical development plans; and other statements that are not historical fact. 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: risks to site initiation, clinical trial commencement, patient enrollment and follow-up, as well as IN8bio’s ability to meet anticipated deadlines and milestones; uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of IN8bio’s product candidates; the risk that IN8bio may be unable to raise additional capital and could be forced to delay, further reduce or to explore other strategic options for certain of our development programs, or even terminate its operations; IN8bio’s ability to continue to operate as a going concern; 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; the uncertainty of 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, are described in greater detail in the section entitled “Risk Factors” in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 12, 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.

Investors & Company Contacts:
IN8bio, Inc.
Patrick McCall
646.933.5603
pfmccall@IN8bio.com

Glenn Schulman, PharmD, MPH
203.494.7411
gdschulman@in8bio.com

Media Contact
Kimberly Ha
KKH Advisors
917.291.5744
kimberly.ha@kkhadvisors.com

FAQ

What are the key advantages of IN8bio's new INB-600 platform over existing TCE therapies?

INB-600 enables sustained γδ T cell expansion up to 450-fold, targets both Vδ1+ and Vδ2+ T cells, and shows lower IL-6 secretion, potentially reducing CRS and neurotoxicity risks.

How does INAB's INB-619 candidate demonstrate efficacy in preclinical models?

INB-619 shows rapid and sustained B-cell depletion through continuous γδ T cell expansion until target cells become undetectable.

What therapeutic areas is IN8bio targeting with the INB-600 platform?

The platform targets both oncology and autoimmune diseases, specifically focusing on leukemias, lymphomas, and autoimmune conditions through CD19 targeting.

What are the next development steps for INAB's INB-619 program?

IN8bio plans to conduct preclinical studies and seek potential partners to support future IND-enabling trials.