For Immediate Release
Keystone Bio

GAIN Trial Results Confirm Relationship Between Porphyromonas gingivalis (Pg) and Alzheimer’s Disease, and Furthers Keystone Bio’s Explanation of Pg’s Toxic Virulence Factors.

gain trial impact Alzheimer's research
The GAIN Trial demonstrated that reduction of Pg infection in the oral cavity results in slowing the progression of Alzheimer’s disease in individuals who are Pg positive (Pg+) in the mouth

[ST. LOUIS, Mo. – Nov 8, 2021] Keystone Bio, a biotechnology company developing precision biologics for the elimination of Pg, acknowledges Cortexyme’s efforts in advancing Alzheimer’s disease research through its recently published Ph ll/lll GAIN Trial preliminary results. Although the trial did not meet its endpoints, it demonstrated that reduction of Pg infection in the oral cavity results in slowing the progression of Alzheimer’s disease in individuals who are Pg positive (Pg+) in the mouth. These results confirm that Pg from the mouth is a cause of some forms of dementia such as Alzheimer’s disease.

“From Keystone Bio’s perspective, the GAIN trial results are a positive advancement relating Pg’s oral source and its removal to the prevention and ultimately the elimination of chronic inflammatory diseases.

said Dr. Daniel Sindelair, DMD, Keystone Bio’s chief executive officer. 

Both Dr. Daniel Sindelar, DMD, Keystone Bio’s chief executive officer and Dr. Peter Nara, Keystone Bio’s Chief Scientific Officer, will be in attendance at the Clinical Trials on Alzheimer’s Disease Conference in Boston this week, the 9-12th and look forward to Cortexyme’s presentation on Thursday of additional top-line data from the trial.

Keystone Bio has identified toxic proteins from Pg in many Alzheimer’s disease brain tissues that are not supported by similar DNA brain tissue studies. Pg toxins leave the mouth, Pg’s only major source, and have to cross the blood brain barrier into the brain, driving forms of early to late dementia including Alzheimer’s disease. These same Pg toxic proteins are reported in high levels in gingival crevicular fluid and as soluble free and immune complexed forms in blood driving vascular inflammation and end organ disease.

Cortexyme’s trial results appear to validate that Pg in the mouth, not the brain, is the key target. Keystone Bio’s own research and disease model, recently published in the Journal of Alzheimer’s Disease, discussed how Pg colonizes the oral cavity and releases tissue-destroying toxic proteins locally and systemically into the bloodstream. Now Keystone Bio is one step closer to connecting this oral driver of neuro-inflammation with the possibility of treating or preventing a major cause of early to late stage dementia and Alzheimer’s disease at its source through a simple diagnostic and precision monoclonal antibody. The GAIN Trial results show that targeting Pg at its source (the mouth) should substantially improve cognitive decline and the progression of Alzheimer’s disease.

Keystone Bio is commercializing a new treatment strategy for diseases driven by Pg’s toxins at their source, the mouth. Keystone Bio’s PrevEvent™ treats Pg and all of its toxins, with the precision monoclonal antibody KB-001. KB-001 was shown in its first clinical trial to prevent recolonization of Pg for 9-12 months in the mouth. Keystone Bio’s collective research demonstrates that individuals with Pg present in their mouth have active Pg-driven systemic inflammatory diseases. Keystone Bio’s monoclonal Antibody KB-001 treats Pg at its source, stopping the flow of the toxic proteins into the bloodstream and ending their impact on multiple chronic inflammatory diseases, which Cortexyme’s results indicate will include Alzheimer’s disease and possibly Parkinson’s disease. Equally important would be the eventual prevention and/or very early treatment and removal of Pg by simple non-invasive delivery of KB-001 at annual dental office visits.

Keystone Bio Recently Published its Explanation of Pg Toxic Virulence Factors in the Journal of Alzheimer’s Disease

Keystone Bio’s research advances that Pg toxic virulence factors that originate in the mouth are primary drivers of chronic inflammatory diseases.

Keystone Bio’s disease model supports a “Peripheral” model of Pg blood-transported toxic proteins where the bacteria itself does NOT cross the Blood Brain Barrier into the brain. Keystone Bio’s model describes Pg establishing a chronic poly-microbial productive biofilm that releases Pg’s toxic protein complexes locally and systemically into the blood and lymphatics, and crosses the BBB into the brain. The toxic protein of Pg that is targeted also drives vascular inflammation and major diseases (such as Alzheimer’s disease and dementia). These Pg toxic proteins therefore must access the brain and both cross the Blood Brain Barrier and lymphatic system of the brain in  yet to be determined levels over a long period of time.

Keystone Bio’s hypothesis paper advancing this model was recently published in the Journal of Alzheimer’s Disease. Read the paper here >.

Keystone Bio’s research and the latest subgroup analysis of the GAIN trial results are positive advancements that relate Pg’s oral source and its removal or prevention to the elimination of chronic inflammatory diseases.

About Keystone Bio 

Keystone Bio is an early clinical stage, biopharmaceutical company developing disease-modifying, precision, anti-bacterial bio-therapeutics to target an important and largely unaddressed bacterial driver of systemic inflammation that significantly contributes to multiple inflammatory diseases, Including Alzheimer’s disease, along with companion diagnostics.

Using Keystone Bio proprietary methods, Keystone Bio has identified a bacterial toxic protein that is a primary driver of systemic inflammation. This bacterial toxic protein complex is secreted actively in large amounts by the Pg bacteria for its own survival; however it produces off-site systemic pathology in various end organs such as the brain, in Alzheimer’s disease brain tissues. This virulent protein complex is packaged into distinct outer membrane vesicles, breaking down and crossing the BBB, and impacting the brain parenchyma in specific neuro-anatomic locations consistent with Alzheimer’s disease development. Those same toxic proteins are delivered throughout the body from their source, spreading systemic inflammation up to and including end-organ disease. Keystone Bio has the only precision biologic that’s been shown to eliminate them at their source. Keystone Bio is also developing the only diagnostic that identifies it in blood.

Keystone Bio is advancing a bio-therapeutic treatment (KB-001 Mab) for the elimination of Pg and all of its virulence factors including the outer membrane vesicles and their toxic protein complex.

Keystone Bio is Backed by Scientists and Medical Professionals with over 35 Years of Experience.

Keystone Bio’s CEO and co-founder Daniel Sindelar, DMD, has played a key role globally in establishing oral pathogens causality of systemic disease including Alzheimer’s for the last 12 years. Dr. Sindelar is the first dental professional to receive a Preceptorship for Heart Attack and Stroke Prevention, is the founder and director of Oral Genomics, LLC.

Peter Nara, formerly Section Chief at the National Cancer Institute and 2011 elected fellow of the American Association for the Advancement of Science (FAAAS), is CSO and co-founder of Keystone Bio. Trained as an infectious disease expert with special scientific interests in novel mechanisms of virulence, pathogenesis, and host adaptation to infectious diseases and cancer, and development of innovative approaches to diagnostic tests, vaccines, and treatments. Dr. Nara has served on many scientific advisory committees and task forces, is an author on more than 125 scientific publications and reviews, and is a co-founder and previously was the president, and CEO of Biological Mimetics (BMI) for almost 20 years and co-founder of Lantern Pharma, a Precision Oncology company.

Forward-Looking Statements

This release cThis release contains estimates, projections and forward-looking statements. The estimates, projections and forward-looking statements contained herein may or may not be realized, and differences between estimated results and those actually realized may be material. Such estimates, projections and forward-looking statements reflect various assumptions of management concerning the future performance of Keystone Bio, and are subject to significant business, economic and competitive uncertainties and contingencies, many of which are beyond the control of Keystone Bio. Accordingly, there can be no assurance that such estimates, projections or forward-looking statements will be realized. No representations or warranties are made as to the accuracy or reasonableness of such assumptions or the projections or forward-looking statements based thereon.

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Contact Keystone Bio

Dr. Daniel Sindelar, DMD, Chief Executive Officer

Email: drd@keystonebio.com

Phone: 314-471-9655

Dr. Peter L. Nara, Chief Scientific Officer

Email: nara@keystonebio.com

Phone: 301-514-4917