Noveome Biotherapeutics is a clinical-stage company focused on developing therapies for the regenerative repair of tissues. Their product ST266, a first-of-its-kind, multi-targeted, non-cellular platform biologic comprised of a complex mixture of biomolecules, is currently being evaluated as a potential treatment for the severe inflammatory response observed in the lungs of some COVID-19 patients. Technology Networks recently spoke with William J. Golden, Noveome Biotherapeutics Founder, Chairman and CEO, who explains the underlying basis for investigating ST266s potential against COVID-19. Golden also elaborates on many of the other indications for which ST266 is being developed to treat. Laura Lansdowne (LL): Could you provide our readers with a brief overview of Noveome Biotherapeutics? William J. Golden (WJG): Noveome is a clinical-stage biotherapeutics company located in Pittsburgh, PA. The company was founded in 2000 by Bill Golden and Lancet Capital. The group was interested in exploring non-embryonic stem cells and identified a technology at the University of Pittsburgh that was using cells derived from human amnion, a membrane that closely covers the fetus during development. The company, named Kytaron Technologies, Inc. at the time, licensed that amnion cell technology but, ultimately, Noveome scientists were able to discover, develop and patent their own unique population of cells, called Amnion-derived Multipotential Progenitor (AMP) cells, using a proprietary culture method that follows current Good Manufacturing Practice (cGMP) regulations. These novel cells were used to produce our product, ST266. LL: What is ST266? Could you elaborate on its mechanism of action in relation to the healing process? WJG: Noveomes product, ST266, is the secretome produced by the AMP cells. It is a completely cell-free solution and is comprised of hundreds of biologically active molecules, including cytokines and growth factors. Interestingly, these cytokines and growth factors exist at very low physiological levels ranging from pg/mL ng/mL concentrations.1 The fact that such low concentrations of these molecules are biologically active is quite remarkable when you consider that traditional protein-based therapies are usually administered at concentrations that are orders of magnitude greater than the concentrations found in ST266. Because the composition of ST266 is so complex, its multiple mechanisms of action have only been partially elucidated. Clinical and preclinical studies have shown ST266 to be anti-inflammatory,2,3 promote wound healing,4,5 reduce apoptosis, reduce vascular permeability (manuscript in preparation), and restore cellular homeostasis.3 Preclinical studies have also shown ST266 to be neuroprotective. In a traumatic brain injury model, ST266 significantly protected against reactive gliosis, suggesting potent anti-inflammatory activity, and resulted in significant recovery of rotarod motor function.6,7 In another study, ST266 was tested in the experimental autoimmune encephalopathy (EAE) mouse model of multiple sclerosis (MS). In this model, the mice develop optic neuritis, which is among the presenting symptoms of MS in humans. ST266 was administered to the nares of mice 15 or 22 days after disease induction. ST266 is absorbed via capillary action along the olfactory nerves which bypasses the blood-brain barrier. This unique route of administration allows for the delivery of high molecular weight biologics to the optic nerve of the eye and the central nervous system. ST266 attenuated visual dysfunction, prevented retinal ganglion cell (RGC) loss, reduced inflammation, and decreased the rate of demyelination of the optic nerve in EAE mice.3Mechanistically, ST266 simultaneously acts on multiple cell receptor-activated and intracellular signaling pathways. For example, in the EAE MS model, neuroprotective effects involved oxidative stress reduction, SIRT1-mediated mitochondrial function promotion, and pAKT signaling.3 In a Phase 2 UV light burn study, ST266 reduced erythema and DNA damage and increased the expression of XPA DNA repair proteins.2Importantly, ST266 has a proven clinical safety profile. It has been administered to 243 patients by various routes of administration (topical skin, topical ocular, topical oral, targeted intranasal), and no drug-related serious adverse events have been reported. Preclinical studies of systemically administered ST266 have also yielded no drug-related safety concerns. LL: For what indications is ST266 currently being evaluated as a treatment? WJG: We refer to ST266 as a platform biologic. By this, we mean that ST266 is one product that has the potential to treat numerous and varied diseases. In the clinic, we have shown anti-inflammatory activity when ST266 is applied topically to UV light-burned the skin2 and topical application to the gums of patients with gingivitis and periodontitis showed a reduction in proinflammatory cytokines in the patients crevicular fluid (manuscript in preparation). We are currently conducting a Phase 2 open label trial of ST266 to treat persistent corneal epithelial defects (PEDs) when applied topically to the eye. Results from this trial will be published soon. We are currently planning a Phase 2b multi-center, randomized, double-masked trial to further evaluate the safety and efficacy of ST266 in this indication. Finally, we are conducting a Phase 1 study in patients at risk for developing glaucoma. This study is using the intranasal route of delivery described above in combination with a novel delivery device. The goal is to deliver ST266 directly to the optic nerve, where it can protect the RGCs that are damaged in glaucoma. We envision this route of delivery will be applicable to central nervous system and other back-of-the eye indications. We also have several ongoing preclinical programs that are evaluating systemically administered ST266 for more generalized inflammatory conditions. These data are not yet published but combined with the data we have compiled in preclinical and clinical studies of topical skin, topical oral and topical ocular administration, we believe ST266 has the potential to be an effective therapy for numerous systemic inflammatory conditions. LL: Could you elaborate on the underlying basis for your evaluation of ST266 as a potential treatment for COVID-19? WJG: As you know, a major complication of COVID-19 is the severe inflammatory response seen in the lungs of some patients. This response is called cytokine storm or cytokine release syndrome. As the pandemic continues and more data have become available, it is now known that the cytokine storm does not just affect the lungs. Multi-organ damage occurs in many of these patients. We believe that systemic delivery of ST266 and its anti-inflammatory activity has the potential to calm the storm. Our as-yet-unpublished preclinical studies with intravenous ST266 support this hypothesis and we are moving rapidly to initiate intravenous ST266 in a Phase 1 study. Once safety in humans is established by this route of administration, we will commence Phase 2 studies in COVID-19 patients. William J. Golden was speaking to Laura Elizabeth Lansdowne, Senior Science Writer for Technology Networks.References
1. Steed, DL, C Trumpower, D Duffy, C Smith, V Marshall, R Rupp, and M Robson. (2008). Amnion-Derived Cellular Cytokine Solution: A Physiological Combination of Cytokines for Wound Healing. Eplasty 8: 15765.
2. Guan, Linna, Amanda Suggs, Emily Galan, Minh Lam, and Elma D. Baron. (2017). Topical Application of ST266 Reduces UV-Induced Skin Damage. Clinical, Cosmetic and Investigational Dermatology. DOI: https://doi.org/10.2147/CCID.S147112.
3. Khan, Reas S, Kimberly Dine, Bailey Bauman, Michael Lorentsen, Lisa Lin, Helayna Brown, Leah R Hanson, et al. (2017). Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model. Scientific Reports. DOI: https://doi.org/10.1038/srep41768.
4. Bergmann, Juri, Florian Hackl, Taro Koyama, Pejman Aflaki, Charlotte a Smith, Martin C Robson, and Elof Eriksson. (2009). The Effect of Amnion-Derived Cellular Cytokine Solution on the Epithelialization of Partial-Thickness Donor Site Wounds in Normal and Streptozotocin-Induced Diabetic Swine. Eplasty 9: e49.
5. Franz, Michael G, Wyatt G Payne, Liyu Xing, D K Naidu, R E Salas, Vivienne S Marshall, C J Trumpower, Charlotte A Smith, David L Steed, and M C Robson. (2008). The Use of Amnion-Derived Cellular Cytokine Solution to Improve Healing in Acute and Chronic Wound Models. Eplasty 8: e21.
6. Deng-Bryant, Ying, Zhiyong Chen, Christopher van der Merwe, Zhilin Liao, Jitendra R Dave, Randall Rupp, Deborah a Shear, and Frank C Tortella. (2012). Long-Term Administration of Amnion-Derived Cellular Cytokine Suspension Promotes Functional Recovery in a Model of Penetrating Ballistic-like Brain Injury. The Journal of Trauma and Acute Care Surgery DOI: https://doi.org/10.1097/TA.0b013e3182625f5f.
7. Deng-Bryant, Ying, Ryan D. Readnower, Lai Yee Leung, Tracy L. Cunningham, Deborah A. Shear, and Frank C. Tortella. (2015). Treatment with Amnion-Derived Cellular Cytokine Solution (ACCS) Induces Persistent Motor Improvement and Ameliorates Neuroinflammation in a Rat Model of Penetrating Ballistic-like Brain Injury. Restorative Neurology and Neuroscience. DOI: https://doi.org/10.3233/RNN-140455.
Continue reading here:
Exploring the Therapeutic Potential of ST266 Against Numerous Diseases Including COVID-19 - Technology Networks
- Hyperbaric Chamber Therapy Brain Injury - May 7th, 2011 [May 7th, 2011]
- Treatment for Traumatic Brain Injury - May 9th, 2011 [May 9th, 2011]
- Atlanta Traumatic Brain Injury Treatment Emory - May 11th, 2011 [May 11th, 2011]
- Hyperbaric Oxygen Therapy Brain Injury Part 2 (Tbi) - May 20th, 2011 [May 20th, 2011]
- Mark, anoxi brain injury, physical therapy after stem cell treatment - May 21st, 2011 [May 21st, 2011]
- Hyperbaric Oxygen Therapy - May 21st, 2011 [May 21st, 2011]
- Bob Hahn Traumatic Brain Injury Recovery - May 23rd, 2011 [May 23rd, 2011]
- Mark, anoxi brain injury, after stem cell treatment at Tiantan Puhua Hospital Beijing - May 24th, 2011 [May 24th, 2011]
- New Beginnings community center for brain injury rehabilitation - May 30th, 2011 [May 30th, 2011]
- Traumatic Brain Injury - Part 1 - Dr. Robert Kohn, Neurologist - June 2nd, 2011 [June 2nd, 2011]
- Am I Brain Damaged? from traumatic brain injury - June 3rd, 2011 [June 3rd, 2011]
- SLI Wellness Center for Brain Injury Rehabilitation - June 11th, 2011 [June 11th, 2011]
- Update on Libya, Radiation in Japan, Tramatic Brain Injury treatment and more, 03/23/2011 - June 12th, 2011 [June 12th, 2011]
- Origami Brain Injury Rehabilitation Center - Finding Your Path - June 12th, 2011 [June 12th, 2011]
- Traumatic Brain Injury - Part 5 - Doctor Kohn, Chicago Neurologist - June 16th, 2011 [June 16th, 2011]
- The struggle to treat traumatic brain injury - June 17th, 2011 [June 17th, 2011]
- Traumatic Brain Injury Survivor Speaks about ProTECT trial at UC Health University Hospital - June 17th, 2011 [June 17th, 2011]
- Stem cell treatment for Brain Injury of Adrian - June 23rd, 2011 [June 23rd, 2011]
- Division of Vocational Rehabilitation Services for Traumatic Brain Injury (TBI) - June 24th, 2011 [June 24th, 2011]
- Hyperbaric Chamber Treatment Stroke and Traumatic Brain Injury TBI - July 4th, 2011 [July 4th, 2011]
- Traumatic Brain Injury - Part 2 - Dr. Robert Kohn, Neurologist - July 6th, 2011 [July 6th, 2011]
- Traumatic Brain Injury - Part 7 - Doctor Kohn, MD, Neurology, Neuropsychiatry - July 14th, 2011 [July 14th, 2011]
- Neurofeedback Training and Treatment at Healing Unleashed in Denver Colorado - July 15th, 2011 [July 15th, 2011]
- Alexis Verzal takes independent steps - July 18th, 2011 [July 18th, 2011]
- The New WalkAide System: Advanced Functional Electrical Stimulation (FES) for Treatment of Foot Drop - July 18th, 2011 [July 18th, 2011]
- Doctors Cool Newborn to Limit Brain Damage - July 19th, 2011 [July 19th, 2011]
- Traumatic Brain Injury - Part 6 - by Neurologist, Dr. Robert Kohn - July 24th, 2011 [July 24th, 2011]
- Brain injury and trauma treatment by homeopathy - July 31st, 2011 [July 31st, 2011]
- Traumatic Brain Injury - Part 4 - Dr. Kohn, Neuropsychiatrist / Neurologist - August 9th, 2011 [August 9th, 2011]
- Preserving Hope, Predicting Health - August 17th, 2011 [August 17th, 2011]
- Sask Brain Injury Association - August 19th, 2011 [August 19th, 2011]
- Cognition and Mild Head Injury by Dr. Muriel Lezak - August 21st, 2011 [August 21st, 2011]
- Brain injury_Shawna_ USA_before stem cell treatment 1.wmv - August 25th, 2011 [August 25th, 2011]
- Origami Brain Injury Rehabilitation Center - Recovery is a Journey - August 26th, 2011 [August 26th, 2011]
- Different types of Concussions by Dr. James Chesnutt.mov - August 30th, 2011 [August 30th, 2011]
- Brain injury_Shawna_ USA_after stem cell treatment 1.wmv - September 11th, 2011 [September 11th, 2011]
- With Brain Injuries, Soldiers Face A Battle For Care - September 23rd, 2011 [September 23rd, 2011]
- Tripler Medical Center Treats Traumatic Brain Injury (TBI) - September 24th, 2011 [September 24th, 2011]
- Sessions' Traumatic Brain Injury Amendment to DOD Appropriations - October 2nd, 2011 [October 2nd, 2011]
- Using Stem Cells for Treatment of TBI | Dr. Charles Cox | Research Trials - October 5th, 2011 [October 5th, 2011]
- Healing brain injuries - October 8th, 2011 [October 8th, 2011]
- Veterans Services at Origami Brain Injury Rehabilitation Center - - October 8th, 2011 [October 8th, 2011]
- Hope Beyond Trauma - October 9th, 2011 [October 9th, 2011]
- Traumatic Brain Injury - Part 3 - by Neurologist Dr. Robert Kohn - October 10th, 2011 [October 10th, 2011]
- Understanding and Improving Vocational Outcomes following Traumatic Brain Injury - Video - October 16th, 2011 [October 16th, 2011]
- LI facility dedicated to Terri Schiavo - Video - October 17th, 2011 [October 17th, 2011]
- Treating Traumatic Brain Injury with Neurotopia - featuring Holden McCray - October 18th, 2011 [October 18th, 2011]
- Brain Injury Survivors: Adriana Villar (Making a Difference: Story 1) - Video - October 21st, 2011 [October 21st, 2011]
- Fabio - brain injury - Video - October 23rd, 2011 [October 23rd, 2011]
- The Latest Developments in Traumatic Brain Injury Treatment - Video - October 25th, 2011 [October 25th, 2011]
- Stem Cell Treatments and Brain Damage Video of MRI of Brain Chambers WWW.STEMCELLREGENMED.COM - Video - October 29th, 2011 [October 29th, 2011]
- Military lags on promising treatment for brain-injured soldiers - Video - November 6th, 2011 [November 6th, 2011]
- Brian Moylan (TBI survivor) talking on treatment from the NHS - Video - November 10th, 2011 [November 10th, 2011]
- Brain Injury Experts at Madonna Rehabilitation Hospital - Video - November 12th, 2011 [November 12th, 2011]
- H200 Hand Rehabilitation System - Testimonials - Clinical Focus - Video - November 13th, 2011 [November 13th, 2011]
- Coping with Brain Injury: Robots and Rehabilitation - Video - November 16th, 2011 [November 16th, 2011]
- Traumatic Brain Injury Rehabilitation using MediTouch HandTutor - Video - November 18th, 2011 [November 18th, 2011]
- Brain Injury Treatment Success | College Station Chiropractor Dr. David Bailey - Video - November 30th, 2011 [November 30th, 2011]
- Hyperbaric Oxygen Therapy (HBOT) corrects brain-injury. - Video - December 7th, 2011 [December 7th, 2011]
- Story of a Traumatic Brain Injury Recovery with Hyperbaric Oxygen (Part1/4) - Video - December 8th, 2011 [December 8th, 2011]
- Hyperbaric Oxygen Therapy Brain Injury - Video - December 10th, 2011 [December 10th, 2011]
- Redwood Extended Care Facility - Brain Injury Services - Video - December 10th, 2011 [December 10th, 2011]
- What If... Brain Injury Rehabilitation - Video - December 17th, 2011 [December 17th, 2011]
- Dangers in Self Medication - Young Adults with Lyme Disease - Leo J. Shea, III, PhD - Video - December 18th, 2011 [December 18th, 2011]
- Reducing Severe Traumatic Brain Injury in the US - Video - December 19th, 2011 [December 19th, 2011]
- Traumatic Brain Injury - Part 8 - Dr. R. Kohn, MD, Neurology - December 21st, 2011 [December 21st, 2011]
- Brain injury rehabilitation using Wii recreational therapy - Video - December 24th, 2011 [December 24th, 2011]
- CNS President/CEO Dr. Mark Ashley discusses how research shapes brain injury rehabilitation - Video - December 29th, 2011 [December 29th, 2011]
- Albert James De Meillon-Traumatic Brain Injury-Part 1 - Video - January 1st, 2012 [January 1st, 2012]
- Hope Beyond Trauma_Janie Smith - Video - January 10th, 2012 [January 10th, 2012]
- Neurofeedback adhd - Video - January 11th, 2012 [January 11th, 2012]
- We are the World, We ARE The Children - Video - January 11th, 2012 [January 11th, 2012]
- New Hopes for Treating Traumatic Brain Injury - Video - January 11th, 2012 [January 11th, 2012]
- NeuroRestorative's Robin Ray Featured on ABC in Southern Illinois - Video - January 13th, 2012 [January 13th, 2012]
- Careers at Origami Brain Injury Rehabilitation Center - Video - January 26th, 2012 [January 26th, 2012]
- Chris Persel discusses what makes CNS a leader in brain injury rehabilitation - Video - January 27th, 2012 [January 27th, 2012]
- Care for catastrophic injuries, spinal cord and traumatic brain injury - Video - January 27th, 2012 [January 27th, 2012]
- Military Tests Pressurized Chamber to Treat TBI - Video - January 27th, 2012 [January 27th, 2012]
- Richmond Traumatic Brain Injury Attorneys Applaud White House Research Initiative Targeting Veterans’ Health Issues - January 28th, 2012 [January 28th, 2012]
- Protect Your Brain...Why? - Video - January 30th, 2012 [January 30th, 2012]