Dr. Daniel Sindelar, DMD CEO and Dr. Peter Nara, D.V.M., Ph.D., FAAAS,CSO/V.P BD, Keystone
Dr. Daniel Sindelar, DMD CEO and Dr. Peter Nara, D.V.M., Ph.D., FAAAS,CSO/V.P BDInflammation is the immediate response of the body to physical trauma, infection, stress, or a combination of all three. However, when it turns out to be self-perpetuating, it becomes chronic and can last for months or even years. This chronic inflammation negatively impacts any and all parts of the body and invites several diseases, including cardiometabolic disease, atherosclerosis, inflammatory cardiovascular disease, stroke, specific cancers, type 2 diabetes mellitus, and neurodegenerative conditions. World Health Organization (WHO) ranks chronic inflammatory-based diseases as the greatest threat to human health. In fact, almost three out of five people die due to these fatal ailments. Such alarming statistic has propelled scientists across the globe to search for the “holy grail” of modern-day medicine that can help them manage this growing incidence of chronic inflammation.

Chronic inflammatory diseases have turned out to be a worldwide epidemic. KB-001 has equipped us with the ability to better help these patients and offer them a better life

Founded in 2018, Keystone Bio—a clinical-stage biopharmaceutical company— is a frontrunner in this space. The company’s foundation is strongly built on the research work of Dr. Daniel Sindelar, DMD, the CEO of Keystone Bio and former President of the American Academy for Oral Systemic Health, and Peter Nara, DVM, PhD., FAAAS, Chief Scientific Officer for Keystone Bio. He always understood the importance of general/specialty dentistry in regards to their patient’s oral health but saw the limitations of traditional care for patients suffering from this fast-emerging, poorly defined oral-systemic health problem. As always is the case in scientific research, the awareness of the problem outpaces the solutions. As such, he sought out and set in place a journey with additional expertise that led to the collaborations with Dr. Garth Ehrlich, Ph.D., FAAAS/SAB, Dr. Marc Penn MD Ph.D., and Dr. Peter Nara, former Section Chief of the National Cancer Institute and Chairman Emeritus/ Past President/CEO/Chairman of the Board of Biological Mimetics Inc.

“The journey started with the simple realization that oral health plays a key role in overall health. Now with over 10,000 research papers on Porphyromonas gingivalis (Pg), it’s become obvious how substantial a role Pg plays in inflammatory and systemic disease. To date, nothing has been found to fully eliminate Pg in a targeted and precision approach to improve chronic inflammatory disease treatments,” says Dr. Sindelar.

Keystone Bio is pioneering novel disease modifying, precision, anti-bacterial therapeutics/preventive along with companion diagnostics to target an important and largely unaddressed bacterial epitope driver of systemic chronic inflammation that significantly contributes to multiple inflammatory disease states, such as heart disease and dementia/Alzheimer’s disease.

Keystone: A New Era Of Inflammatory-Based Disease Treatment

The Unique Discovery by Keystone Bio

To be specific, Keystone Bio has discovered a one-of-a-kind virulent subunit protein complex in neuro-anatomic strategic sites of AD brain tissues. The bacterial toxic protein complex is secreted actively in large amounts by Pg for its own survival and crosses the blood-brain barrier (BBB). Thus, it impacts the brain parenchyma in specific neuro-anatomic locations. Typically, these toxic proteins are delivered throughout the body from their oral source. This results in a chronic low-grade infection that disrupts our immune system and spreads systematic inflammation up to and including end-organ disease. Keystone Bio’s lead bio-therapeutic is KB-001 monoclonal antibody inactivates and eliminates both the SOURCE and the secreted toxins. “Chronic inflammatory diseases have turned out to be a worldwide epidemic. KB-001 has equipped us with the ability to better help these patients and offer them a better life,” adds Dr. Nara.

  • We have delineated a well-mapped-out plan of clinical trials to introduce our biotherapeutic and diagnostics to market as fast as possible for addressing the unmet needs

KB-001 disrupts the later stages of the major protein surface processing machinery. For the uninitiated, Pg is an evolutionary anomaly that returns one week after regular dental cleaning and re-establishes its bio-film 30 days after non-surgical periodontal treatment. It can even be present in a visually clean, healthy-looking mouth. This can lead to a slow, low to high levels of local and systematic damage without a person even noticing. KB-001 prevents Pg from creating its secreted outer membrane vesicles (OMVs), resulting in the bacteria shutting down its metabolic and host defense functions. “KB-001 has the capability to treat Pg and of its virulence factors,” adds Dr. Nara.

Changing the Face of the Healthcare

There is perhaps no doubt that KB-001 will bridge the gap between a dentist, a general and specialty internal medical practitioners (e.g., cardiology, primary care) as both will be able to use this drug to treat and prevent inflammatory-based diseases. Also, this monoclonal antibody will equip healthcare providers with the capability to stop any disease at this early stage or even its arrival. “KB-001 has the capability to change the paradigm of medicine in which a single infectious agent is responsible for causing more than one disease. By treating a single agent, one is able to treat more than one disease. This would be revolutionary and make treatment incredibly efficient and accessible to a larger patient-base. Not to mention, this will be extremely feasible from a cost standpoint,” says Dr. Ehrlich. “We have delineated a well-mapped-out plan of clinical trials to introduce our biotherapeutic and diagnostics to market as fast as possible for addressing the unmet needs.”

KB-001 has already undergone the phase-1 clinical trial process where its unique binding capability to Pg toxin/survival complex was proved before the world. Currently, they are expecting to make KB-001 available under the guidance of possible fast-track FDA approval.

The founders of Keystone Bio Inc. are excited for the second set of clinical trials of the antibody bio-therapeutic through their Australian subsidiary in the second quarter of 2021. They will be duplicating a study that was already performed in humans—duplicating some of the same clinical endpoints while expanding with new ones. The company is also currently conducting its translational research throughout the U.S., Europe, and India. “We are constantly looking for and developing new insight and methods to identify other “Pg-like organisms” that may also be present in the body and prove to be fatal,” adds Dr. Ehrlich.

The Pipeline of Innovation

Keystone Bio is currently developing two precision diagnostics to further identify the pathogen in its early stages of infection - KBd-001 and KBd-002. While the former helps in comparing Pg’s genomic profile with other biological assays to find the most infectious type, they can check the blood plasma to search for the protein that has a similar composition as the toxic subset. Such tests can help medical personnel in finding the pathogen and start early treatment. Keystone Bio has also developed two human chimeric monoclonal antibodies—KBhu-007 and KBhu- 0014—as different drug delivery methods for possible systemic dosing. More importantly, they are currently en route to introduce KBvx-001, a vaccine that can prevent Pg onset in the first place. “We are calling Pg a biological extremophile as it can live and thrive under an array of host responses and a dynamic biological environment such as exists in the oral cavity while silently damaging in our critical physiological systems. We know its mechanism at a molecular level. That’s why our precision guided monoclonal antibody will help people live healthier lives,” concludes Dr. Nara.