Pipeline

Ernexa Therapeutics is building a pipeline of off-the-shelf, synthetic cell therapies designed to modulate the immune system and restore balance in the face of disease. Our lead candidates target high-need areas in oncology and autoimmune conditions, with a focus on delivering powerful, tissue-targeted treatments that can scale.

ERNA-101 (Ovarian Cancer)

Ovarian cancer remains the deadliest gynecologic cancer, with most cases diagnosed at an advanced stage. Additionally, an alarming 85% of patients experience recurrence after standard treatment. Despite advances in chemotherapy and targeted therapies, outcomes for patients with platinum-resistant disease remain poor, highlighting a major unmet need.

Immune checkpoint inhibitors have shown limited success in ovarian cancer. This is likely due to the immunosuppressive tumor microenvironment, which blocks immune cell function and limits therapy effectiveness.

Ernexa Therapeutics’ lead program, ERNA-101, is designed to overcome these challenges by remodeling the tumor microenvironment to support a stronger immune response. 
Our approach builds on the foundational work of world-renowned expert Michael Andreeff, M.D., Ph.D., from The University of Texas MD Anderson Cancer Center. Dr. Andreeff’s studies showed that engineered mesenchymal stem cells (MSCs) can successfully home to tumor sites, deliver immunostimulatory molecules, and reduce tumor burden in preclinical ovarian cancer models.

We believe this strategy, using engineered iMSCs to deliver targeted immune activation, represents a promising and scalable new path forward for patients with ovarian cancer.

References

  1. Siegel, R.L., et al., Cancer statistics, 2022. CA Cancer J Clin, 2022. 72(1): p. 7-33.
  2. Goff, B., Symptoms associated with ovarian cancer. Clin Obstet Gynecol, 2012. 55(1): p. 36-42.
  3. Peres, L.C., et al., Invasive Epithelial Ovarian Cancer Survival by Histotype and Disease Stage. J Natl Cancer Inst, 2019. 111(1): p. 60-68.
  4. Torkildsen, C.F., et al., New immune phenotypes for treatment response in high-grade serous ovarian carcinoma patients. Front Immunol, 2024. 15: p. 1394497.
  5. Hao, J., et al., Prognostic impact of tumor-infiltrating lymphocytes in high grade serous ovarian cancer: a systematic review and meta-analysis. Ther Adv Med Oncol, 2020. 12: p. 1758835920967241.
  6. Ovarian Tumor Tissue Analysis, C., et al., Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer. JAMA Oncol, 2017. 3(12): p. e173290.
  7. Sato, E., et al., Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A, 2005. 102(51): p. 18538-43.
  8. Bobisse, S., et al., Sensitive and frequent identification of high avidity neo-epitope specific CD8 (+) T cells in immunotherapy-naive ovarian cancer. Nat Commun, 2018. 9(1): p. 1092.
  9. Nelson, B.H., et al., Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer. J Clin Invest, 2024.
  10. Shalaby, A., et al., Correlation of PD-L1 expression with different clinico-pathological and immunohistochemical features of ovarian surface epithelial tumors. Clin Transl Oncol, 2024.
  11. Varga, A., et al., Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Gynecol Oncol, 2019. 152(2): p. 243-250.
  12. Hamanishi, J., et al., Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA). J Clin Oncol, 2021. 39(33): p. 3671-3681.
  13. Hensler, M., et al., M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer. J Immunother Cancer, 2020. 8(2).
  14. Fu, W., Q. Feng, and R. Tao, Machine learning developed a fibroblast-related signature for predicting clinical outcome and drug sensitivity in ovarian cancer. Medicine (Baltimore), 2024. 103(16): p. e37783.
  15. Desbois, M., et al., Integrated digital pathology and transcriptome analysis identifies molecular mediators of T-cell exclusion in ovarian cancer. Nat Commun, 2020. 11(1): p. 5583.
  16. Dembinski, J.L., et al., Tumor stroma engraftment of gene-modified mesenchymal stem cells as anti-tumor therapy against ovarian cancer. Cytotherapy, 2013. 15(1): p. 20-32.
  17. Olson, A., et al., A Phase I Trial of Mesenchymal Stem Cells Transfected with a Plasmid Secreting Interferon Beta in Advanced Ovarian Cancer. Biology of Blood and Marrow Transplantation, 2018. 24(3): p. S473.

ERNA-201 (Rheumatoid Arthritis)

Rheumatoid arthritis is a common and debilitating autoimmune disease that affects roughly 18 million people worldwide, 70% of whom are women. While current treatments can manage symptoms for many, a substantial number of patients – especially those with difficult-to-treat rheumatoid arthritis – continue to suffer from chronic inflammation and joint damage.

Cell-based therapies, including mesenchymal stem cells (MSCs), have shown early promise in reducing inflammation and improving symptoms in both preclinical and early clinical studies. However, the efficacy of MSCs has been limited due to challenges with variability, manufacturing complexity, and suboptimal targeting of the inflammation site.

Ernexa Therapeutics’ candidate, ERNA-201, overcomes these challenges by leveraging synthetic MSCs derived from induced pluripotent stem cells (iPSCs). This engineered approach delivers the potent anti-inflammatory cytokine IL-10 directly to the site of inflammation, with superior consistency, enhanced functionality, and more precise targeting. 

By resetting the inflammatory environment of the joints, ERNA-201 has the potential to provide more potent, lasting disease control for patients who need it most.

References

1. Black, R.J., et al., Global, regional, and national burden of rheumatoid arthritis, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. The Lancet Rheumatology, 2023. 5(10): p. e594-e610.

2. Li, Y.J. and Z. Chen, Cell-based therapies for rheumatoid arthritis: opportunities and challenges. Ther Adv Musculoskelet Dis, 2022. 14: p. 1759720X221100294.

3. Rai, V., et al., Futuristic Novel Therapeutic Approaches in the Treatment of Rheumatoid Arthritis. Cureus, 2023. 15(11): p. e49738.

4. He, N., et al., Mesenchymal stem cell-derived extracellular vesicles targeting irradiated intestine exert therapeutic effects. Theranostics, 2024. 14(14): p. 5492-5511.

5. Shimizu, Y., et al., Optimizing mesenchymal stem cell extracellular vesicles for chronic wound healing: Bioengineering, standardization, and safety. Regen Ther, 2024. 26: p. 260-274.

6. Stoppelenburg, A.J., et al., Design of TOLERANT: phase I/II safety assessment of intranodal administration of HSP70/mB29a self-peptide antigen-loaded autologous tolerogenic dendritic cells in patients with rheumatoid arthritis. BMJ Open, 2024. 14(9): p. e078231.

7. Nam, Y., et al., Intraperitoneal infusion of mesenchymal stem cell attenuates severity of collagen antibody induced arthritis. PLoS One, 2018. 13(6): p. e0198740.

8. Shu, J., et al., Transplantation of human amnion mesenchymal cells attenuates the disease development in rats with collagen-induced arthritis. Clin Exp Rheumatol, 2015. 33(4): p. 484-90.

9. Li, X., et al., Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor. Front Cell Dev Biol, 2020. 8: p. 131.

10. Abdelmawgoud, H. and A. Saleh, Anti-inflammatory and antioxidant effects of mesenchymal and hematopoietic stem cells in a rheumatoid arthritis rat model. Adv Clin Exp Med, 2018. 27(7): p. 873-880.

11. Jung, N., et al., LC-MS/MS-based serum proteomics reveals a distinctive signature in a rheumatoid arthritis mouse model after treatment with mesenchymal stem cells. PLoS One, 2022. 17(11): p. e0277218.

12. El-Gendy, H., et al., Comparative study between human mesenchymal stem cells and etanercept as immunomodulatory agents in rat model of rheumatoid arthritis. Immunol Res, 2020. 68(5): p. 255-268.

13. Yang, Y., et al., Serum IFN-gamma levels predict the therapeutic effect of mesenchymal stem cell transplantation in active rheumatoid arthritis. J Transl Med, 2018. 16(1): p. 165.

14. Wang, L., et al., Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cell Therapy for Rheumatoid Arthritis Patients: A Prospective Phase I/II Study. Drug Des Devel Ther, 2019. 13: p. 4331-4340.

15. Alvaro-Gracia, J.M., et al., Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (Cx611): results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase Ib/IIa clinical trial. Ann Rheum Dis, 2017. 76(1): p. 196-202.