IDP-023 is a highly potent natural killer cell platform under evaluation for patients with multiple myeloma and non-Hodgkin lymphoma.
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Indapta Therapeutics has received FDA Fast Track Designation for its natural killer (NK) cell therapy IDP-023 for patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL).1 The company’s universal, allogeneic NK cell therapy platform is comprised of a potent subset of naturally occurring NK cells called G minus NK (g-NK) cells.
In clinical research, these cells have demonstrated significantly superior killing capacity than conventional NK cells without requiring genetic engineering of the cells. For manufacturing of IDP-023, Indapta extracts g-NK cells from healthy donors with greater numbers of g-NK cells and low donor-to-donor variability.2
“This designation highlights the promise of Indapta’s highly potent NK cell platform and will further accelerate clinical development of our lead drug candidate, IDP-023, for two of the largest unmet needs in B-cell driven blood cancers, NHL and multiple myeloma,” said Mark Frohlich, MD, chief executive officer of Indapta Therapeutics, in a press release.1
Preclinical research has shown that IDP-023 produces more potent and durable antitumor activity than cancer-targeting monoclonal antibodies (mAbs) compared to conventional NK cells.
“(mAbs) are a central component of therapy for hematologic malignancies. Widely used mAb agents in (MM) include daratumumab and elotuzumab. However, not all patients respond to these agents, and resistance is a significant clinical issue,” wrote the authors of a study published by Blood Advances. “A recently discovered subset of human natural killer (NK) cells lacking expression of FcεRIγ (g-NK cells) was found to have a multifold increase in antibody-dependent effector functions after CD16 crosslinking.”3
For the study, the researchers evaluated the ability of g-NK cells to improve the efficacy of mAbs against MM. An in vitro analysis suggested that g-NK cells combined with daratumumab or elotuzumab have significantly superior anti-myeloma cytotoxicity compared with conventional NK cells.
An evaluation of in vivo efficacy found combining daratumumab and g-NK cells produced a >99.9% tumor reduction compared with daratumumab combined with conventional NK cells. Further, the daratumumab plus g-NK cells combination completely eradicated the myeloma burden in five of seven mice.
“It is noteworthy that the combination of g-NK cells with daratumumab was able to completely eliminate tumor in a disseminated orthotopic xenograft MM.1S model of MM,” the study authors wrote. “We are currently focusing on larger-scale expansion and donor standardization to create a clinical-grade product for evaluation in human trials. In conclusion, we propose that this novel NK cell therapy could be administered in an off-the-shelf manner to supercharge mAb efficacy in MM and eventually other malignancies as well.”3
Indapta Therapeutics began treating the first patients with IDP-023 in January 2024 at NEXT Oncology in Virginia and The University of Texas MD Anderson Cancer Center in Houston.4 The first patient enrolled in the study was administered a single dose of IDP-023, with a second patient administered the first of three planned doses. Additional patient groups will receive three doses of the drug with or without IL-2.
References
1. Indapta Therapeutics receives U.S. FDA fast track designation for lead clinical drug candidate IDP-023 for non-Hodgkin’s lymphoma and myeloma. News release. Indapta Therapeutics. February 29, 2024. Accessed February 29, 2024. https://www.businesswire.com/news/home/20240229681905/en
2. Allogeneic natural killer cells IDP-023. National Cancer Institute. Accessed February 29, 2024. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/allogeneic-natural-killer-cells-idp-023
3. Austin B. Bigley, Shanae Spade, Nadia H. Agha, Sujit Biswas, Suni Tang, Muhammad H. Malik, Lu Dai, Shalaleh Masoumi, Bonell Patiño-Escobar, Martina Hale, Guy DiPierro, Ronald Martell, Byron Hann, Nina Shah, Arun P. Wiita, Xinli Liu; FcεRIγ-negative NK cells persist in vivo and enhance efficacy of therapeutic monoclonal antibodies in multiple myeloma. Blood Adv 2021; 5 (15): 3021–3031. doi: https://doi.org/10.1182/bloodadvances.2020002440
4. Indapta Therapeutics announces first patients treated with IDP-023 allogeneic natural killer (NK) cell therapy for cancer. News release. Indapta Therapeutics. January 11, 2024. Accessed February 29, 2024. https://www.businesswire.com/news/home/20240111941372/en/Indapta-Therapeutics-Announces-First-Patients-Treated-with-IDP-023-Allogeneic-Natural-Killer-NK-Cell-Therapy-for-Cancer
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