Indapta Therapeutics Showcases Promising Clinical Activity of IDP-023 Allogeneic g-NK Cell Therapy in Relapsed/Refractory Multiple Myeloma at SITC 2025
Indapta Therapeutics, Inc., a privately held, clinical-stage biotechnology company focused on developing next-generation immunotherapies for cancer and autoimmune disease, has presented new early-phase clinical data demonstrating the activity of its novel allogeneic g-NK (g-minus natural killer) cell therapy, IDP-023, in patients with relapsed/refractory multiple myeloma (R/R MM). The therapy was evaluated both as a monotherapy and in combination with isatuximab, an approved anti-CD38 monoclonal antibody (mAb) widely used in multiple myeloma treatment.
These findings contribute to a growing body of evidence demonstrating the potential of allogeneic NK-cell-based immunotherapies as transformative options for heavily pretreated patients who have exhausted available lines of care. The company’s data were Allogeneic presented during the Society for Immunotherapy of Cancer (SITC) Annual Meeting, held November 7–9, 2025, in Washington, D.C., under Abstract #1322, titled:
“IDP-023 Allogeneic g-NK-cells +/- Anti-CD38 Monoclonal Antibody for the Treatment of Relapsed/Refractory Multiple Myeloma: Safety, Efficacy and Determination of Recommended Phase 2 Dose.”
The abstract details outcomes from the safety run-in portion of an ongoing Phase 1 clinical trial, as well as observations from the initial patient cohort receiving IDP-023 combined with an anti-CD38 antibody.
Executive Leadership Perspective
In discussing the results, Mark Frohlich, MD, Chief Executive Officer of Indapta Therapeutics, emphasized the significance of these findings given the advanced disease state and complexity of patients treated:
“We are encouraged to observe this degree of clinical activity of IDP-023 alone and in combination with isatuximab. This is particularly noteworthy given the extent of prior therapies and adverse prognostic features of the patients treated. We look forward to treating additional patients to better characterize the response proportion and durability of treatment effect.”
His remarks underscore the challenges associated with improving outcomes for relapsed/refractory multiple myeloma, particularly in those who have previously undergone numerous treatment regimens—including targeted, cellular, and biologic therapies—and may exhibit aggressive disease features.
Understanding the Clinical Context: Relapsed/Refractory Multiple Myeloma
Multiple myeloma is an incurable plasma cell malignancy characterized by dysfunctional antibody-producing cells and progressive bone marrow failure. Despite advances in immunotherapeutic modalities, including proteasome inhibitors, immunomodulatory agents, anti-CD38 monoclonal antibodies, bispecific T-cell engagers, and Allogeneic autologous CAR-T therapy, most patients eventually relapse. Once they become refractory to multiple drug classes—including monoclonal antibodies and CAR-T treatments—therapeutic options become severely limited, and prognosis worsens significantly.
High-risk cytogenetics, extramedullary disease, and short duration of response to prior therapies further complicate disease management. Allogeneic Therefore, new modalities—especially those not reliant on patient-derived cells and demonstrating robust activity—are urgently needed.
Study Design and Treatment Regimens
IDP-023 was administered to participants in the ongoing Phase 1 safety run-in either:
- Alone (as monotherapy), or
- In combination with isatuximab
Patients received one to three doses of IDP-023, with or without interleukin-2 (IL-2) supplementation, which is occasionally used to support NK cell survival and proliferation in vivo. The study incorporates dose escalation, and the results presented pertain primarily to patients treated at the 10-billion-cell dose level, with a focus on defining the recommended Phase 2 dose (RP2D).
This design enables assessment of safety, tolerability, preliminary activity, and potential dose-response relationships. Particularly relevant is the Allogeneic ability to evaluate whether combination therapy with an anti-CD38 mAb may enhance NK-cell-mediated cytotoxicity via mechanisms such as antibody-dependent cellular cytotoxicity (ADCC).
Key Clinical Findings
1. Tumor Reduction Observed Across Treatment Arms
Meaningful tumor shrinkage was reported in both groups—patients receiving IDP-023 alone and those treated in combination with isatuximab. This early indication of efficacy supports the concept that epigenetically enhanced g-NK cells may exert direct antitumor activity independent of antibody engagement, while also benefiting from antibody-mediated targeting.
2. Strong Results at Higher Cell Dose in Combination Cohort
A notable response rate was observed among patients treated at the 10-billion-cell dose level combined with isatuximab:
- 4 of 5 response-evaluable patients demonstrated confirmed responses.
Importantly, these individuals were heavily pre-treated and displayed high-risk or ultra-high-risk cytogenetic features, suggesting IDP-023 may retain activity in biologically aggressive disease settings where other advanced therapies have failed.
3. Deep Response in Patient with Extensive Prior Therapy
One of the most compelling outcomes involved a patient with:
- Extramedullary disease, and
- Prior progression after CAR-T therapy and T-cell engager therapy
This patient achieved a stringent complete response (sCR) following treatment with IDP-023 and isatuximab. Achieving deep responses after failure of multiple Allogeneic cellular immunotherapies is rare, underscoring the potential of g-NK cell therapies to overcome immunoresistance.
4. Improved Responses with Repeat IDP-023 Cycles
An additional observation suggests that administering a second cycle of IDP-023 in combination with isatuximab may enhance both:
- Depth of response, and
- Durability of clinical benefit
If validated in more patients, this could influence future dosing strategies and support continued dosing beyond initial treatment cycles.
5. Favorable Safety Profile
Treatment was generally well tolerated:
- No dose-limiting toxicities (DLTs) reported
- Most common adverse events were cytopenias, attributed primarily to conditioning chemotherapy
The absence of major safety signals is noteworthy for an allogeneic NK-cell therapy, as such products must be carefully monitored for risks including cytokine release syndrome, graft-versus-host-disease (GvHD), and Allogeneic severe immune-related toxicities. The preliminary safety findings suggest that IDP-023 may be suitable for combination strategies and repeated dosing.
Indapta’s Proprietary g-NK Cell Platform
IDP-023 is derived from Indapta’s universal, allogeneic NK-cell platform, which isolates and expands a unique population of NK cells known as “g-minus NK cells” or “g-NK cells.” These cells arise due to epigenetic modification triggered by prior exposure to cytomegalovirus (CMV) in donors. CMV exposure can prime NK cells, creating a memory-like effector population with enhanced cytotoxic properties.
To manufacture IDP-023:
- g-NK cells are isolated from healthy donors
- The cells are expanded ex vivo
- Final product batches exhibit low donor-to-donor variability
The resulting allogeneic product is designed to deliver consistently potent NK-cell activity independent of genetic modification.
Mechanisms of Action Driving g-NK Potency
g-NK cells show improved functionality Allogeneic due to their unique receptor and cytokine expression profiles. IDP-023 leverages multiple killing mechanisms, including:
1. Antibody-Dependent Cellular Cytotoxicity (ADCC)
- NK cells bind to antibodies attached to the surface of cancer cells
- This enhances targeted tumor killing
- Combining IDP-023 with isatuximab likely amplifies ADCC-mediated clearance of CD38-positive myeloma cells
2. Targeting of HLA-E-Expressing Cells via NKG2C
- NKG2C receptor binds HLA-E, which is often upregulated on tumor cells
- This interaction enables selective recognition and elimination
- This is particularly valuable in cases where tumors downregulate classical HLA molecules to evade adaptive immune surveillance
3. Intrinsic Antiviral and Cytokine-Release Capabilities
- g-NK cells retain strong antiviral properties
- They release high levels of immune-activating cytokines and cytotoxic granules
- Compared with conventional NK cells, they can unleash more powerful and sustained antitumor immune responses
These mechanisms collectively enable broad targeting of malignant cells without the need for genetic editing, simplifying manufacturing and potentially improving safety compared to engineered cell therapies.
Supporting Evidence from Preclinical Studies
As referenced in preclinical findings published in Blood Advances (Bigley et al., 2021), IDP-023 demonstrated:
- More potent and durable antitumor activity than conventional NK cells
- Increased cytotoxicity when combined with tumor-specific antibodies
- Ability to deplete normal B cells when paired with B-cell-targeting antibodies
These findings support the clinical exploration of IDP-023 in both cancer and autoimmune indications, as B-cell depletion may be beneficial in certain autoimmune pathologies.
Potential Advantages of the IDP-023 Approach
Allogeneic NK-cell therapies aim to overcome the logistical and therapeutic limitations of current T-cell–based approaches, including CAR-T therapies, which require:
- Patient-specific manufacturing
- Extended production time
- Complex conditioning regimens
- Potentially severe toxicities
By contrast, IDP-023:
- Is derived from healthy donors
- Can be manufactured at scale
- Has off-the-shelf availability
- Demonstrates multi-mechanistic tumor targeting
- Shows early signals of tolerability
Such features could offer a more accessible, rapidly deployable immunotherapy option for patients with aggressive disease requiring quick intervention.
The results shared at SITC represent early but encouraging evidence supporting IDP-023’s further clinical development. Over the coming phases of the trial, Indapta intends to:
- Enroll additional patients across dose levels
- Further assess durability of responses
- Evaluate repeat-cycle benefits
- Continue exploring combination strategies with monoclonal antibodies and additional agents
Defining the recommended Phase 2 dose will be a key milestone, enabling broader expansion into later-phase studies designed to evaluate efficacy more rigorously.
If subsequent studies validate these early findings, IDP-023 could emerge as a compelling treatment option for multiple myeloma patients who relapse after existing standard therapies—including CAR-T and T-cell engagers—an area where treatment innovation is especially needed.
Indapta Therapeutics’ early clinical data with IDP-023, a novel allogeneic g-NK cell therapy, provide promising evidence of clinical activity and manageable safety in a highly pretreated relapsed/refractory multiple myeloma population. Responses observed—particularly a stringent complete response in a patient who had previously progressed after CAR-T and T-cell engagement therapies—underscore the potential clinical value of g-NK-based therapeutics.
With favorable safety, early signals of durable responses, and multi-modal mechanisms of action, IDP-023 represents an innovative addition to the rapidly evolving field of cellular immunotherapy. The findings support continued clinical investigation, including expanded cohorts and combination strategies, as the company advances toward Phase 2 development.
As interest in off-the-shelf NK-cell products continues to accelerate, Indapta’s g-NK cell platform may help shape the next generation of accessible, effective therapies for hematologic malignancies and potentially autoimmune diseases.
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