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Landmark data positions ERNA-101 as a potential game-changing immunotherapy and a major catalyst for future clinical and shareholder value
CAMBRIDGE, Mass., May 06, 2026 — Ernexa Therapeutics (Nasdaq: ERNA), an industry innovator developing novel cell therapies for the treatment of advanced cancer and autoimmune disease, today announced new preclinical data demonstrating that its lead cell therapy candidate, ERNA-101, in combination with PD-1 blockade, drives complete tumor clearance and 100% long-term survival in syngeneic ovarian cancer models.
“This data represents a significant step forward,” said Robert H. Pierce, M.D., Chief Scientific Officer of Ernexa Therapeutics. “We are not just seeing strong response, we are seeing complete tumor eradication and durable survival, driven by a powerful immune activation mechanism within the tumor itself. These findings underscore the potential of ERNA-101 to overcome one of the biggest challenges in ovarian cancer – an immunologically ‘cold’ TME – and to unlock the full potential of checkpoint inhibition. Subsequent to a positive clinical proof-of-concept trial in collaboration with the MD Anderson Cancer Center in platinum-resistant ovarian cancer, we anticipate broadening the scope of indications to include other solid tumors, where strong immunosuppression in the tumor microenvironment limits the clinical benefit of anti-PD-1 therapy.”
In the study, treatment with ERNA-101 in combination with anti-PD-1 therapy resulted in complete tumor clearance (i.e., loss of detectable tumor signal by bioluminescence imaging) and 100% survival through long-term follow-up. These outcomes significantly exceeded those observed with either therapy alone and suggest potential curative activity.
The data further demonstrate that ERNA-101 remodels the TME from immunosuppressive to immune-activated, enabling robust and sustained anti-tumor immune responses.
“What we are seeing goes beyond expectations. Achieving complete tumor elimination and 100% survival in a model where current approaches typically fall short reinforces both the strength of the data and the underlying mechanism driving this response. These results give us increased confidence in ERNA-101’s ability to meaningfully enhance the activity of checkpoint inhibitors and potentially shift treatment outcomes in ovarian cancer. This approach may also extend beyond ovarian cancer, with the potential to drive meaningful responses across other immunologically ‘cold’ solid tumors characterized by highly suppressive tumor microenvironments. We believe ERNA-101 has the potential to become a foundational therapy in combination regimens, significantly expanding treatment effectiveness,” said Sanjeev Luther, President and Chief Executive Officer of Ernexa Therapeutics.
ERNA-101 is an allogeneic induced mesenchymal stem cell (iMSC) therapy derived from induced pluripotent stem cells (iPSCs) and engineered to home to tumors and secrete a potent IL-7/IL-15 fusion cytokine directly within the TME. This localized cytokine delivery approach is designed to maximize immune activation while minimizing systemic toxicity.
Key findings from the preclinical studies include:
- Complete tumor clearance and survival: Combination therapy eliminated detectable tumors and achieved 100% survival in treated mice through long-term follow-up
- Tumor microenvironment remodeling: ERNA-101 converted the tumor environment from immunosuppressive to immune-activated, enabling stronger immune attack on the tumor
- Enhanced immune cell activity: Treatment increased the activity, survival, and persistence of key cancer-fighting T cells
- Immune infiltration: Significantly more CD4⁺ and CD8⁺ T cells were able to enter tumors and engage cancer cells directly
- Macrophage reprogramming: Immune cells within the tumor shifted toward a cancer-fighting state rather than a tumor-supporting state
- Reduced disease burden: Treatment reduced tumor burden and decreased ascites fluid accumulation associated with advanced disease
Ovarian cancer, particularly high-grade serous ovarian carcinoma (HGSOC), remains a significant unmet medical need, with most patients diagnosed at advanced stages and high relapse rates following standard therapies. Existing treatments, including checkpoint inhibitors, have shown limited efficacy due to the highly immunosuppressive TME.
Ernexa plans to incorporate these findings into its development strategy as it advances ERNA-101 toward a first-in-human clinical trial in patients with advanced ovarian cancer. Ongoing studies are evaluating ERNA-101 in combination with checkpoint inhibitors and other immuno-oncology agents.
About Ernexa Therapeutics
Ernexa Therapeutics (NASDAQ: ERNA) is developing innovative stem cell therapies for the treatment of advanced cancer and autoimmune disease. Ernexa’s core technology focuses on engineering induced pluripotent stem cells (iPSCs) and transforming them into induced mesenchymal stem cells (iMSCs). Ernexa’s synthetic, allogeneic iMSCs provide a scalable, off-the-shelf treatment, without needing patient-specific cell harvesting.
ERNA-101 is the company’s lead cell therapy product, designed to activate and regulate the immune system’s response to recognize and attack cancer cells. ERNA-201 is a cell therapy product designed to target inflammation and treat autoimmune disease. The company’s initial focus is to develop ERNA-101 for the treatment of ovarian cancer.
Ernexa’s synthetic, allogeneic iMSCs could also be used to treat glioblastoma and other brain tumors if they also use IntrepiCyte’s noninvasive intranasal method of cell delivery and targeting as described here.
Intranasal anti-inflammatory stem cells and immune cells bypass the blood-brain barrier to treat Parkinson’s, Alzheimer’s, Brain Tumors, TBI & Stroke.
Together with my collaborators in Germany, especially Lusine Danielyan M.D., we discovered and patented (1) that therapeutic cells, including stem cells, migratory immune cells (T cells, microglia, macrophages, etc.) and genetically-engineered cells, can be delivered to the brain using the noninvasive intranasal delivery method that I developed (2). The first of our scientific papers on this new discovery describes this successful method of delivery and proprietary formulations that enhance delivery (3). The second of our papers describes the treatment of Parkinson’s disease in an animal model with intranasal adult bone marrow derived mesenchymal stem cells (4). Intranasal stem cells bypass the blood-brain barrier to target the brain by traveling extracellularly along the olfactory neural pathway with minimal delivery to other organs. Once in the brain, adult stem cells specifically target the damaged areas of the brain where they reduce neuroinflammation and treat the underlying disease (4). Researchers in Malaysia, China and Taiwan have recently also demonstrated the intranasal treatment of animal models of Parkinson’s disease using dental pulp stem cells (5), bone marrow-derived MSCs (6), MSCs overexpressing FGF21 (6a) and bone marrow stromal cells (7). Researchers in Iran have reported the intranasal treatment of an animal model of Parkinson’s using olfactory mucosa stem cells (8) and endometrial stem cells (9). Preclinical studies suggest that intranasal stem cell treatment is safe (10). Dr. Simorgh et al. reported the magnetic targeting of intranasal human olfactory mucosa stem cells to treat a rat model of Parkinson’s (11). A clinical trial was reported in which four Parkinson’s patients were treated with both intranasal (into the submucous layer of the olfactory epithelium) and intravenous stem cells (12). The authors state, autologous MSC administration is safe and has beneficial effects, but it is not known to what extent the intranasal cells contributed in relation to the intravenously administered cells in this one pilot human study (12). Intranasal human umbilical stem cells treat a mouse model of Parkinson’s disease (13). Intranasal human olfactory stem cells also treat a rat model of Parkinson’s disease (14).
Also see the important work of Dr. van Velthoven and other researchers at University Medical Center Utrecht in the Netherlands who have demonstrated the effectiveness of intranasal stem cell treatment technology in an animal model of neonatal cerebral ischemia (15, 16), neonatal stroke (17) and also in animals with neonatal hypoxia-ischemia brain damage (18, 19, 20, 21, 22) and subarachnoid hemorrhage (23, 24). Nijboer et al. reported that CXCL10 is a crucial chemoattractant for efficient intranasal delivery of mesenchymal stem cells to the neonatal hypoxic-ischemic brain (24a). Researchers in Germany demonstrated delayed intranasal stem cell treatment improved motor deficits and cognitive function in mice with neonatal hypoxic-ischemic brain injury (25). Researchers in China have demonstrated the effectiveness of intranasal human neural stem cell treatment of hypoxic–ischemic encephalopathy in neonatal rats (26) and of human amniotic stem cells in hypoxic-ischemic encephalopathy in neonatal mice (26a). Intranasal human umbilical cord stem cells help to treat global hypoxic ischemia in neonatal pigs (27) and neonatal rats (28, 29). Researchers in Russia have demonstrated the beneficial effects of intranasal implantation of mesenchymal stem cells on nitric monoxide levels in the hippocampus, control of cognitive functions, and motor activity in rats with cerebral ischemia (31). Researchers in Switzerland have demonstrated intranasal umbilical cord-derived stem cells preserve myelination in perinatal brain damage (30) and researchers in the Netherlands boosted myelination after encephalopathy of prematurity with intranasal MSCs (32). Researchers at Emory University and others have used our intranasal stem cell treatment successfully in animal models of stroke (33, 34, 35, 36) and neonatal stroke (37, 38), and researchers at Uppsala University in Sweden have demonstrated that intranasal CAR/FoxP3-engineered T regulatory cells efficiently suppressed ongoing inflammation in an EAE model of multiple sclerosis leading to reduced disease symptoms (39). Intranasal human oligodendrocyte lineage cells migrate preferentially to niches of OPCs in the brains of mice as shown by researchers from Mexico and Spain (40). Intranasal adult neural stem cells have also been shown to improve the EAE model of multiple sclerosis (MS) (41) as have intranasal mesenchymal stromal cells (42). Another research group in China has reported that intranasal Fasudil‐modified encephalitogenic mononuclear cells (MNCs) delays the onset and ameliorates the severity in EAE mouse model of MS, accompanied by improvement of demyelination (43). Intranasal SDF‐1α‐preconditioned bone marrow MSCs also improved remyelination in the cuprizone‐induced mouse model of multiple sclerosis (44). Intranasal delivery of adipose MSCs to the corpus callosum maintained the structure of the corpus callosum and prevented demyelination in the CPZ model of MS in female mice (44a). Other researchers have reported that intranasal stem cells target and treat brain tumors (45, 46, 47, 48, 49, 50, 51, 52) and protect against neurologic complications of radiotherapy (53) and chemotherapy induced peripheral neuropathy (54). Intranasal cells have been successfully used to shuttle an oncolytic adenovirus to treat glioblastoma in mice (54a), and a hepatic stellate cell line has been developed for intranasal delivery of therapeutic cargo to the central nervous system (54b). Intranasally administered mesenchymal stem cells have also been shown to transfer their mitochondria to neural stem cells to increase brain cell energy (55).
This intranasal delivery, targeting and treatment technology can make stem cell treatments practical for brain disorders by eliminating the need for invasive neurosurgical implantation of cells and by eliminating the need for intravenous delivery that disperses cells throughout the body resulting in unwanted systemic exposure. This delivery and treatment method can facilitate the development of stem cell, immune cell, microglia, macrophage and genetically-engineered cell therapies for Parkinson’s, PSP, Huntington’s (56, 57), Alzheimer’s (58, 59, 59a, 59b), MS, epilepsy, stroke, neonatal ischemia, brain tumors (59c), traumatic brain injury (TBI) (60, 61, 61a), spinal cord injury (62), drug addiction (63, 64) and even LSDs such as Niemann-Pick-type C disease (65).
Intranasal anti-inflammatory stem cells are also of interest in treating COVID-19 which initially accumulates in the nasal cavity. In addition to its adverse effects on the lungs which lead to ARDS, SARS-CoV-2, and even more often its inflammatory cytokine storm, can also transport from the nose into the brain contributing to problems with anosmia, brain fog, mood disorders, sleep disruption and potentially even oxygen sensing in the medulla and difficulty breathing. (See: Meinhardt et al. (2020) Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19, Nature Neuroscience.) In addition to acute inflammatory brain damage, there will also likely be long-term neurological consequences to COVID-19 which intranasal anti-inflammatory stem cells can address. Note that some of those who survived the 1918 viral pandemic went on years later to develop Parkinson’s disease. Intranasal anti-inflammatory stem cells delivered directly to the area where the virus accumulates in the nose may help to treat and perhaps even prevent both acute and long-term brain damage associated with COVID-19 and its pro-inflammatory cytokine storm. Intranasal adult stem cells can potentially function as the firetrucks chasing after the pro-inflammatory cytokine storm as these peptides migrate along the olfactory and trigeminal pathways into the brain. Numerous studies have shown in both animals and humans that intranasal peptides bypass the blood-brain barrier by traveling directly from the nasal cavity into the brain along the olfactory and trigeminal neural pathways.
In humans, Gonadotropin-releasing hormone expressing neurons are known to reach the brain by using this same olfactory neural pathway during development. In addition, pathologic cells, such as the amoeba Naegleria fowleri, are known to enter the brains of humans by this same pathway and cause amoebic infection of the brain. We have discovered how to use this pathway to deliver therapeutic cells to the brain to treat brain disorders (66). Danielyan et al. (67) have recently reported that selecting stem cells with superior cell motility and increased migratory potential can improve the therapeutic benefit achieved following intranasal stem cell treatment.
In 2022, Baak et al (68) published a first-in-human study demonstrating that intranasal bone marrow-derived MSC administration in neonates after perinatal arterial ischaemic stroke is feasible with no serious adverse events observed in patients followed up to 3 months of age. This study follows a clinical observation paper reporting that the brain injury area of preterm infants with intracranial hemorrhage reduced significantly following intranasal treatment with breast milk (including breast milk stem cells and nutritional factors) (69). Recently, researchers in China published a paper entitled Safety and Efficacy Outcomes after Intranasal Administration of Neural Stem Cells in Cerebral Palsy: a randomized controlled trial which reported that “Compared to the control group, patients in the treatment group showed apparent improvements in GMFM-88 and ADL 24 months after treatment. Compared with the baseline, the scale scores of the Fine Motor Function, Sociability, Life Adaptability, Expressive Ability, GMFM-88, and ADL increased significantly in the treatment group 24 months after treatment, while the SDSC score decreased considerably. Compared with baseline, the FBN analysis showed a substantial decrease in brain network energy, and the VBM analysis showed a significant increase in gray matter volume in the treatment group after NSCs treatment.” (70). Additional clinical trials of intranasal stem cells for brain disorders are planned, and a detailed study protocol for a randomised controlled trial in ischaemic stroke was published (71). A recent phase 1 clinical trial in people with advanced Parkinson’s showed not only safety but also preliminary efficacy with functional improvement in clinical outcomes with peak efficacy achieved at month six (72). [See the final attached PDF.]
Contact us with any questions you may have about non-invasive intranasal delivery and targeting of therapeutic cells to the CNS to treat neurological, psychiatric and behavioral disorders. We can help you deliver and target your cells specifically to the diseased and damaged areas of the CNS.
Best Regards,
Bill
William H. Frey II, Ph.D., CEO
IntrepiCyte, LLC
[email protected]
http://www.intrepicyte.com
Cell phone: 651-261-1998
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Best regards,
Bill
William H. Frey II, Ph.D., CEO
IntrepiCyte, LLC
St. Paul, MN USA
[email protected]
http://www.intrepicyte.com
Cell phone: 651-261-1998