IN8bio’s Announces Peer-Reviewed Publication of Preclinical Results Using Proprietary MGMT-modified Gamma-Delta T Cells (INB-200) with Temozolomide in Mouse Models of Glioblastoma Multiforme

Rhea-AI Summary

IN8bio announced significant survival benefits from concurrent dosing of MGMT-modified gamma-delta T cells with Temozolomide (TMZ) in high-grade glioma models. The findings, published in Scientific Reports, support the clinical development of the company’s Drug Resistant Immunotherapy (DRI) technology. Currently, a Phase 1 trial is evaluating DRI with TMZ in glioblastoma multiforme at the University of Alabama at Birmingham. This approach aims to enhance tumor response while maintaining immune functionality.

Positive

• Significant survival benefit demonstrated in mice using concurrent dosing of MGMT-modified gamma-delta T cells and Temozolomide.
• Strong preclinical support for the clinical development of DRI for newly diagnosed glioblastoma.
• Phase 1 clinical trial currently underway at O’Neal Comprehensive Cancer Center.

Negative

• None.

Concurrent dosing of MGMT-modified gamma-delta T cells with Temozolomide (TMZ) demonstrated a significant survival benefit across multiple models of high-grade glioma

MGMT-modified gamma-delta T cells are engineered to survive chemotherapy and form the basis of IN8bio’s Drug Resistant Immunotherapy (DRI) technology

These results, published online in the Nature portfolio journal Scientific Reports (DOI: https://doi.org/10.1038/s41598-021-00536-8), provide significant preclinical support for the clinical development of DRI

DRI with a concurrent TMZ dosing regimen is currently being evaluated in a Phase 1 clinical trial in glioblastoma multiforme (GBM) at the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham (UAB)

NEW YORK, Oct. 27, 2021 (GLOBE NEWSWIRE) -- IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company focused on the discovery and development of innovative gamma-delta T cell therapies utilizing its DeltEx platform, today announced the peer-reviewed publication of preclinical results that provides foundational support for the use of DRI in newly diagnosed GBM. This work, published in the Nature portfolio journal Scientific Reports, focused on the use of gamma-delta T cells genetically engineered to be chemotherapy resistant through the addition of an O6-Methylguanine-DNA Methyltransferase (MGMT) transgene, a process termed Drug Resistant Immunotherapy (or DRI). Concurrent dosing of DRI cells with TMZ resulted in a significant improvement in survival outcomes in mice over either monotherapy alone in both classical and mesenchymal primary high-grade gliomas.

These studies were performed by IN8bio’s scientific co-founder and Chief Scientific Officer, Dr. Lawrence Lamb while at UAB, in collaboration with researchers at Emory University, and the technology has been exclusively licensed world-wide by IN8bio. This unique technology forms the basis for the company’s DeltEx DRI platform, which utilizes ex-vivo expanded, activated gamma-delta T cells that can be engineered to be chemotherapy resistant for both solid and liquid tumors. This preclinical work provides support for the concurrent dosing of DRI cells with TMZ to debulk the tumor, reduce accumulation of immunosuppressive cells and upregulate innate effector cell activation through an increase in NKG2D-ligands. This approach is currently undergoing evaluation in a Phase 1 trial in patients with newly diagnosed GBM at The University of Alabama at Birmingham.

“Chemotherapeutic agents, including TMZ can upregulate stress induced ligands in tumor cells, which can be recognized by gamma-delta T cells,” said Lawrence S. Lamb, Ph.D., Chief Scientific Officer, co-founder of IN8bio and the lead author of the paper. “Unfortunately, TMZ is lymphodepleting, hindering the immune system’s ability to leverage this state of increased tumor vulnerability. To overcome this, we developed gamma-delta T cells engineered with a gene conferring resistance to alkylating agents such as TMZ, allowing our MGMT-modified cells to remain functional through concurrent administration. We observed that this concomitant combination resulted in a significant improvement in survival over either monotherapy or sequential therapy and we are now evaluating this regimen in clinical trials.”

William Ho, Chief Executive Officer and co-founder of IN8bio said, “This approach, which forms the basis for IN8bio’s DeltEx DRI programs targets an evolutionarily conserved pathway, the DNA Damage Response (or DDR), that has potential applicability across a broad range of solid tumors for which chemotherapy remains the mainstay of treatment. This includes potentially combining INB-200 with other approaches such as checkpoint inhibitors and other targeted therapies in orthogonal combinations to maximize the tumor impact. Combined with our expertise in genetically engineering these cells ex-vivo, we look forward to continuing to develop our deep pipeline of gamma-delta T cell based therapies for cancer.”

About IN8bio
IN8bio is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of gamma-delta T cell product candidates for solid and liquid tumors. 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. IN8bio’s DeltEx platform employs allogeneic, autologous and genetically modified approaches to develop cell therapies, designed to effectively identify and eradicate tumor cells.

IN8bio is currently conducting two investigator-initiated Phase 1 clinical trials for its lead gamma-delta T cell product candidates: INB-200 for the treatment of newly diagnosed glioblastoma and INB-100 for the treatment of patients with leukemia undergoing hematopoietic stem cell transplantation. IN8bio also has a broad portfolio of preclinical programs focused on addressing other solid tumor types.

For more information about IN8bio and its programs, please visit www.IN8bio.com.

Forward Looking Statements
Certain statements herein concerning the Company’s future expectations, plans and prospects, including without limitation, the Company’s current expectations regarding the advancement of its product candidates through preclinical studies and clinical trials and the prospects for such candidates and underlying technology, constitute forward-looking statements under the Private Securities Litigation Reform Act of 1995. The use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” the negative of these and other similar expressions are intended to identify such forward looking statements. Such statements, based as they are on the current expectations of management, inherently involve numerous risks and uncertainties, known and unknown, many of which are beyond the Company’s control. Consequently, actual future results may differ materially from the anticipated results expressed in such statements. Specific risks which could cause actual results to differ materially from the Company’s current expectations include: scientific, regulatory and technical developments; failure to demonstrate safety, tolerability and efficacy; final and quality controlled verification of data and the related analyses; expense and uncertainty of obtaining regulatory approval, including from the U.S. Food and Drug Administration; and the Company’s reliance on third parties, including licensors and clinical research organizations. Do not place undue reliance on any forward-looking statements included herein, which speak only as of the date hereof and which the Company is under no obligation to update or revise as a result of any event, circumstances or otherwise, unless required by applicable law.

Company Contact:
IN8bio, Inc.
Kate Rochlin, Ph.D.
+1 646.600.6GDT (6438)
info@IN8bio.com

Investors:
Solebury Trout
David Buck
+ 1 646.378.2927
dbuck@soleburytrout.com 

Media:
Burns McClellan, Inc.
Robert Flamm, Ph.D. / Harrison Wong
+1 212.213.0006 - ext. 364 / 316
rflamm@burnsmc.com / hwong@burnsmc.com

FAQ

What are the results of IN8bio's recent study on gamma-delta T cells and Temozolomide?

IN8bio's study showed significant survival benefits when gamma-delta T cells modified with MGMT were dosed concurrently with Temozolomide in high-grade glioma models.

When is the Phase 1 clinical trial for DRI expected to conclude?

The timeline for the Phase 1 clinical trial's conclusion is not specified, but it is currently ongoing at the University of Alabama at Birmingham.

How does DRI improve treatment outcomes for glioblastoma patients?

DRI aims to enhance tumor response by allowing gamma-delta T cells to remain functional during Temozolomide treatment, combating immunosuppression.

What is IN8bio's focus with its Drug Resistant Immunotherapy technology?

IN8bio's DRI technology focuses on developing gamma-delta T cell therapies that are engineered to survive chemotherapy and target solid tumors.

What is the significance of the findings published in Scientific Reports?

The findings provide essential preclinical support for developing DRI therapies for newly diagnosed glioblastoma, indicating potential clinical efficacy.