Summary: NLS Pharmaceutics and Kadimastem plan to merge to develop multi-target therapies for diabetes-associated neurological and sleep disorders, leveraging NLS’s DOXA platform—integrating orexin signaling, neuroprotection, and metabolic regulation—as a potential disease-modifying treatment beyond glucose control.
Key Takeaways:
- Research underscores the connection between diabetes, neurodegeneration, and sleep disorders, collectively termed diabetes-associated neurological and sleep disorders
- Unlike GLP-1 receptor agonists that primarily target blood sugar, DOXA integrates orexin signaling, neuroprotection, and metabolic regulation to address systemic complications, including sleep-wake disturbances.
- A paradigm shift in diabetes care, integrating sleep medicine with metabolic and neurological management, may be on the horizon.
Diabetes is more than a metabolic disorder—it is a multi-systemic disease affecting the central nervous system, immune function, and cellular metabolism. A growing body of research highlights the connection between diabetes, neurodegeneration, and sleep disorders, collectively known as diabetes-associated neurological and sleep disorders.
An upcoming expected merger between NLS Pharmaceutics Ltd and Kadimastem Ltd aims to address these complex interactions that the companies posit require a paradigm shift toward multi-target therapeutic strategies.
NLS Pharmaceutics is a Swiss clinical-stage biopharmaceutical company focused on the discovery and development of innovative therapies for rare and complex central nervous system disorders, and Kadimastem is a clinical-stage cell therapy company developing and manufacturing “off-the-shelf” allogeneic cell products for the treatment of neurodegenerative diseases and potential cure for diabetes. By uniting the core competencies of both organizations, NLS and Kadimastem believe that this merger is positioned to potentially create a holistic solution that addresses the multifaceted challenges of diabetes management.
Introducing DOXA: A Multi-Target Innovation for Diabetes
NLS is pioneering DOXA (dual orexin and multi-pathway modulation), a therapeutic approach integrating orexin receptor agonism, neuroprotective pathways, and metabolic regulation to holistically manage diabetes and its systemic complications.
Unlike conventional approaches that primarily target incretin signaling, DOXA leverages multi-target mechanisms to synchronize metabolic and neurological pathways by acting on:
- orexin signaling (OX1R/OX2R): aiming to restore energy balance, cognitive function, and metabolic stability, counteracting diabetes-related fatigue and neurodegeneration;
- sigma-1 receptor (Sig-1R) modulation: aiming to reduce oxidative stress, neuroinflammation, and insulin resistance, critical factors in diabetes complications;
- cathepsin Inhibition (CTSS/CTSL): aiming to protect neuronal integrity and β-cell survival, crucial for long-term metabolic health;
- sodium-glucose cotransporter-2 (SGLT2) modulation: aiming to improve glucose metabolism while reducing neuropathic and vascular damage; and
- adiponectin receptor activation: Aiming to enhance insulin sensitivity and mitochondrial function, addressing core metabolic dysfunctions.
Findings to Be Presented at American Society of Clinical Psychopharmacology 2025
Preclinical studies to be presented at the 2025 American Society of Clinical Psychopharmacology Annual Meeting provide evidence that DOXA compounds:
- restore orexinergic function, improving metabolic balance and sleep-wake disturbances;
- reduce inflammatory markers and neurodegeneration, preventing diabetes-induced neuronal damage; and
- Enhance β-cell survival and glucose metabolism, positioning DOXA as a disease-modifying therapy rather than a glucose-dependent intervention.
Possible Complement to GLP-1s
“I believe that this next-generation diabetes treatment must go beyond glucose control. While GLP-1 therapies address part of the problem, they fail to target the neurological and systemic disruptions linked to the disease, including diabetes-associated neurological and sleep disorders,” says Eric Konofal, MD, PhD, chief scientific officer of NLS and inventor behind DOXA, in a release. “At NLS, our DOXA platform aims to integrate neuroscience, metabolism, and regenerative medicine. Combined with Islet transplantation, we anticipate a breakthrough—enhancing insulin sensitivity, metabolic regulation, and long-term disease modification.”
Alex Zwyer, CEO of NLS, adds in a release, “This planned merger represents a remarkable opportunity to combine our strengths and expertise. Together, believe that we will advance innovative solutions to better address the challenges of diabetes and related disorders, delivering enhanced value to patients.”
Ronen Twito, executive chairman and CEO of Kadimastem, says in a release, “We are thrilled about the upcoming merger, which aligns our strategic goals and is aimed at empowering us to provide comprehensive therapeutic options. By joining forces, we believe that we will be well-equipped to tackle the complexities of diabetes and improve outcomes for those we serve.”
