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Sublingual NAD+ is the new gold standard for daily NAD+ supplementation, without the need for precursors SINGAPORE, Sept. 1, 2024 /PRNewswire/ -- iX Biopharma (the " Company"), a specialty pharmaceutical company specializing in drug delivery systems and a leader in innovative healthspan nutraceuticals, has announced groundbreaking results from a pharmacokinetic study evaluating the sublingual absorption of a novel NAD+ wafer, SL-NAD+. This study is the first to provide compelling evidence that NAD+ can directly enter cells, offering a promising new approach to NAD+ supplementation. The study consisted of 3 parts: 2 single-dose PK studies and a multiple-dose PK study, conducted in 18 Sprague-Dawley rats, examining the plasma and red blood cell NAD+ levels following sublingual administration of NAD+. Assessment of NAD+ levels were done via the LC-MS/MS method, one of the most advanced and reliable methods to test for NAD+. The results revealed several important findings: First evidence of direct cellular entry : The study strongly suggests that NAD+ can be transported in and out of cells directly (NAD+ flux), most probably via connexin 43 hemichannels and other solute carrier channels. This is the first in-vivo study to provide evidence supporting this capability. Rapid sublingual absorption: Mean peak plasma concentration, a 2-fold increase in plasma NAD+ levels, was achieved within 10 minutes of dosing. This underscores the effectiveness of sublingual delivery through the mucosa. Significant bioavailability : The findings suggest a sublingual bioavailability of SL-NAD+ at 22% compared to intravenous (IV) administration. This provides a promising alternative to IV NAD+ therapy, with the potential for more convenient and sustained NAD+ delivery. Dr. Janakan Krishnarajah, Chief Operating Officer and Chief Medical Officer of iX Biopharma, said: "This study's findings provide strong evidence that our innovative sublingual freeze-dried technology delivers NAD+ rapidly into plasma and then directly into cells, challenging the previously held belief that its large size prevents cellular penetration. Along with the positive data from our recent human clinical study, this breakthrough positions direct NAD+ supplementation as the new gold standard for boosting NAD+ levels, removing the need for precursors." About NAD+ and SL-NAD+ NAD (nicotinamide adenine dinucleotide) is a critical molecule in our body responsible for vital cellular functions in the body. It is crucial for energy production, cellular metabolism, DNA repair, regulating sleep cycles and promoting healthy aging. NAD+ levels decrease as we age, with levels typically dropping to half by the time we reach 50. The decline in NAD+ levels with age is linked to various age-related health concerns and metabolic disorders. In recent years, NAD+ has become an important focus in scientific research on aging, with maintenance of adequate NAD+ levels being linked to healthy aging and longevity. Clinical trials have also been conducted to investigate the potential of NAD+ in treating various age-related diseases, such as Type 2 Diabetes, Non-Alcoholic Fatty Liver Disease, neurodegenerative diseases like Parkinson's disease, cardiovascular and skeletal muscle diseases. Despite its potential, NAD+ has been challenging to utilise effectively, other than through IV. Alternative ways to boost NAD+ levels with NAD precursors, like NMN and NR, may be inefficient due to bioavailability and other issues, such as inefficient conversion to NAD+ due to age-related declines in enzyme activity. SL-NAD+ is a novel sublingual wafer that delivers NAD+ directly into the bloodstream, bypassing the digestive system to ensure higher bioavailability and significantly boosting intracellular NAD+ levels. The Company's proprietary freeze-drying process and patented wafer formulation stabilises NAD+ and delivers them as nanoparticles, ensuring rapid disintegration, release, and absorption through the sublingual mucosa. SL-NAD+ is available for purchase on and through select specialist clinics in Singapore. About iX Biopharma Ltd iX Biopharma is a specialty pharmaceutical and nutraceutical company listed on the Catalist board of the Singapore Exchange Securities Trading Limited (SGX-ST), operating a fully integrated business model from drug development to manufacturing and supply, with facilities in Australia. The Group is focused on the development and commercialisation of pharmaceutical drugs and innovative nutraceuticals using novel, patent-protected formulations for sublingual delivery. iX Biopharma has developed a number of drug delivery platform technologies, including WaferiX, WaferlogiX and NADiX, which deliver small molecule and biologics sublingually via the mucosa for better absorption, faster onset of action and predictable effect. The drug delivery platforms are particularly useful for drug repurposing, where existing approved drugs are developed into new drugs targeting different indications or a different route of administration, at a lower development cost and risk. iX Biopharma's portfolio includes among others, ketamine, dexmedetomidine, medicinal cannabis and nutraceuticals designed to improve healthspan and longevity. SOURCE iX Biopharma

– Presentation Will Highlight Positive Clinical Trial Data on iNexin™ for Treatment of Corneal Injury – – Xequel Launches New Corporate Website with Focus on Novel Peptide Platform for Ophthalmology, Dermatology and Pulmonology – Charleston, SC and Fort Worth, TX, September 27, 2022 – Xequel Bio, Inc., a clinical stage biopharmaceutical company developing ophthalmic and dermatologic therapeutics utilizing its patented new chemical entity aCT1 (alpha-Connexin carboxyl-Terminal 1 peptide), announced today that Jerry St. Peter, Chief Executive Officer, will present a corporate overview and new iNexin™ (aCT1 ophthalmic solution) clinical data at the Eyecelerator conference on September 29, 2022, as part of the Annual Meeting of the American Academy of Ophthalmology (AAO) in Chicago, IL. AAO is the world’s largest association of eye physicians and surgeons. “We are excited to highlight the breadth of our novel platform across multiple indications involving inflammation and the body’s response to injury,” said Jerry St. Peter, Chief Executive Officer and Board Member. “In clinical and preclinical studies for the front of the eye, iNexin demonstrated acceleration of corneal healing and restoration of the ocular surface.” “Most notably, we plan to present new data from our recently completed positive Phase 1b study of iNexin for the treatment of corneal injury in patients with moderate to severe dry eye. This study demonstrated that iNexin was safe and well-tolerated and early efficacy signals were observed at the doses tested, providing the rationale to advance to Phase 2,” continued Mr. St. Peter. “Xequel is well-positioned for future growth and value creation by leveraging our deep R&D expertise, proprietary platform and strong patent portfolio. We have just launched a redesigned website, www.xequel.com, that captures our vision for pioneering the science of technology and innovation to provide patient solutions in ophthalmology, dermatology, and pulmonology,” Mr. St. Peter concluded. Eyecelerator @ AAO 2022 Therapeutics Showcase Presentation Presenting Company Showcase: Therapeutics Date/Time: Thursday, September 29, 2022, 3:19 PM CDT Location: McCormick Place Convention Center, Chicago Presenter: Jerry St. Peter, Chief Executive Officer and Board Member About Eyecelerator Eyecelerator is a partnership between the American Academy of Ophthalmology (AAO) and the American Society of Cataract and Refractive Surgery (ASCRS) to advance innovation in eye care by connecting mission-driven entrepreneurs, investors, physicians, and global strategic executives through next-generation business conferences. For more information, visit www.eyecelerator.com. About Xequel’s aCT1 Technology Platform Xequel Bio’s aCT1 (alpha-Connexin carboxyl-Terminal 1 peptide) technology platform is designed to develop drugs that will enable physicians to better manage a variety of indications involving inflammation and the body’s response to injury. aCT1 is a patented new chemical entity, based on the C-terminal sequence of Connexin43, designed to selectively and reversibly inhibit protein binding of endogenous Connexin43 to key binding partners. Connexin43 plays critical roles in multiple aspects of the injury response, including spread of injury signals, extravasation of immune cells, granulation tissue formation and fibrosis. aCT1’s unique, targeted mechanism of action has been demonstrated to restore the coordination of cellular communication, reinforce junctional integrity and temper excessive inflammatory responses in injured tissues for optimal injury response and tissue repair. aCT1 is currently in clinical development for multiple indications across dermatology and ophthalmology, as well as in ongoing preclinical research in pulmonology. About Xequel Bio, Inc. Xequel Bio, Inc. is a clinical stage biopharmaceutical company advancing its proprietary aCT1 (alpha-Connexin carboxyl-Terminal 1 peptide) technology platform to develop drugs that will enable physicians to better manage a variety of indications involving inflammation and the body’s response to injury. aCT1 is a patented new chemical entity currently in development for multiple indications. The Company’s lead clinical programs include Granexin® gel in dermatology and iNexinTM ophthalmic solution in ophthalmology. The Company also has ongoing preclinical research in pulmonology. For more information, please visit www.xequel.com. Contacts: Wes Brazell, Chief Financial Officer, Xequel Bio, Inc. Jenny Kobin, IR Advisory Solutions Info@xequel.com Source: Xequel Bio, Inc. 777 Taylor Street Suite 1140 Fort Worth, Texas 76102 info@xequel.com 1501 Belle Isle Avenue Suite 220 Mount Pleasant, South Carolina 29464 843.388.3276 Privacy Policy | Accessibility Statement Powered by Website Muscle

Excellent Safety and Tolerability Profile for iNexin™ for the Treatment of Corneal Injury Early Efficacy Signals Provide Rationale to Advance to Phase 2 Proprietary aCT1 Platform to Address Unmet Needs for Patients with Ophthalmic Diseases Charleston, SCand Fort Worth, TX, July 14, 2022 –Xequel Bio, Inc., a clinical stage biopharmaceutical company developing ophthalmic and dermatologic therapeutics utilizing its patented new chemical entity aCT1 (alpha-Connexin carboxyl-Terminal 1 peptide), announced positive results from its Phase 1b clinical trial with iNexin™ (aCT1 ophthalmic solution) for the treatment of corneal injury in patients with dry eye disease. The study demonstrated that iNexin was safe and well-tolerated at the doses tested, and early efficacy signals were observed. This Phase 1b trial was a single-center, randomized, double masked, vehicle-controlled clinical study to assess the safety and exploratory efficacy of iNexin for the treatment of corneal injury in patients with dry eye disease. There were no serious adverse events or dose-limiting toxicities associated with iNexin treatment. Improvements in both signs (e.g., corneal staining) and symptoms (e.g., ocular discomfort) of dry eye disease were observed within two weeks of treatment in both the environment and Ora’s controlled adverse environment (CAE®) model, which exacerbates signs and symptoms of dry eye disease in a safe and standardized manner for greater precision in predicting treatment efficacy. “These results support our belief that iNexin, our novel aCT1 ophthalmic solution, has the potential to improve patient outcomes by regulating the inflammatory response to promote improved ocular healing,” said Jerry St. Peter, Chief Executive Officer. “We are extremely pleased that the key goals of this study were met, providing clinical evidence of safety, tolerability, and also early signs of efficacy in patients with corneal injury. This data provides a strong basis to further refine our therapeutic focus and dosing regimen as we progress our ophthalmic development program, including designing our Phase 2 clinical trial.” Dr. Gail Torkildsen, MD, board certified ophthalmologist at Andover Eye Associates, said “This study provides an initial look at the safety, tolerability, and potential biological activity of iNexin in treating dry eye disease, with a mechanism of action suggesting additional application in treating ocular injury and inflammation. The results are encouraging and indicate the potential for aCT1 to restore Connexin43, which plays a critical role in the inflammatory cascade. iNexin could represent an innovative solution to treat patients with corneal injuries by promoting healing and rebuilding healthy tissue through accelerated re-epithelialization.” This Phase 1b trial was a single-center, randomized, double masked, vehicle-controlled clinical study to assess the safety and exploratory efficacy of iNexin compared to Vehicle in patients with dry eye disease. A total of 36 participants, with a subject-reported history of dry eye disease in both eyes, were enrolled and randomized in a 2:1 allocation for each of three concentrations of iNexin (0.08%; 0.4%; 2.0% aCT1) to Vehicle (eye drop formulation without aCT1), administered bilaterally twice a day for 14 days. The primary objective of the trial was to evaluate the safety and tolerability of iNexin. The secondary objective was to compare the efficacy of iNexin to Vehicle for the treatment of the signs and symptoms associated with dry eye disease. This trial was managed and monitored by Ora, Inc., a leading full-service ophthalmic drug and device development firm, and was supported by the Department of Defense Defense Health Program, Congressionally Directed Medical Research Program through Vision Research Program Award W81XWH-20-1-0879. About Xequel’s aCT1 Technology Platform Xequel Bio’s aCT1 (alpha-Connexin carboxyl-Terminal 1 peptide) technology platform is designed to develop drugs that will enable physicians to better manage a variety of indications involving inflammation and the body’s response to injury. aCT1 is a patented new chemical entity, based on the C-terminal sequence of Connexin43, designed to selectively and reversibly inhibit protein binding of endogenous Connexin43 to key binding partners. Connexin43 plays critical roles in multiple aspects of the injury response, including spread of injury signals, extravasation of immune cells, granulation tissue formation and fibrosis. aCT1’s unique, targeted mechanism of action has been demonstrated to restore the coordination of cellular communication, reinforce junctional integrity and temper excessive inflammatory responses in injured tissues for optimal injury response and tissue repair. aCT1 is currently in clinical development for multiple indications across dermatology and ophthalmology, as well as in ongoing preclinical research in pulmonology. About Xequel Bio, Inc. Xequel Bio, Inc. is a clinical stage biopharmaceutical company advancing its proprietary aCT1 (alpha-Connexin carboxyl-Terminal 1 peptide) technology platform to develop drugs that will enable physicians to better manage a variety of indications involving inflammation and the body’s response to injury. aCT1 is a patented new chemical entity currently in development for multiple indications. The Company’s lead clinical programs include Granexin® gel in dermatology and iNexin™ ophthalmic solution in ophthalmology. The Company also has ongoing preclinical research in pulmonology. For more information, please visit www.xequel.com. About Ora, Inc. Ora is the world’s leading full-service ophthalmic drug and device development firm. For over 40 years, their expert teams have proudly helped clients across the globe earn more than 55 product approvals. Ora’s unique methodologies and strategies have been proven across thousands of programs to maximize the likelihood of success and efficiently bring new products from concept to market. For more information, please visit www.oraclinical.com. Contacts: Wes Brazell, Chief Financial Officer, Xequel Bio, Inc. Jenny Kobin, IR Advisory Solutions info@xequel.com 777 Taylor Street Suite 1140 Fort Worth, Texas 76102 info@xequel.com 1501 Belle Isle Avenue Suite 220 Mount Pleasant, South Carolina 29464 843.388.3276 Privacy Policy | Accessibility Statement Powered by Website Muscle