NIA Small Business Showcase: Praetego

Praetego is pioneering a groundbreaking class of drugs known as Amadorins, with a mission to protect patients from age-related diseases. The primary focus is on developing a therapeutic that is potent, oral, cost-effective, and specifically designed to thwart neurodegeneration. Praetego is committed to altering the impact of Alzheimer’s disease (AD), thereby enhancing the overall aging experience.

AD/dementia affects 1 in 9 adults over age 65, and diabetes affects 1 in 4. Someone with diabetes diagnosed before age 60 is three times more likely to develop AD/dementia. An oral drug for early intervention could radically alter the aging experience.

Praetego’s innovation mitigates the impact of advanced glycation end products (AGEs), commonly referred to as glycotoxins, generated during the essential process of glucose metabolism. AGEs wreak havoc on the body as it ages, with their formation accelerated under hyperglycemic conditions such as those seen in diabetes. AGEs promote aberrant protein aggregation, chronic inflammation, oxidative stress, and ultimately organ damage. Praetego’s Amadorins act as a powerful counterforce, inhibiting AGE formation and acting as a deterrent to serious diabetic complications, AD, and other age-related diseases.

Praetego’s Amadorins have demonstrated potential for the treatment of Alzheimer’s disease. The Amadorins are potent small molecules uniquely targeting the oxidation of glycated proteins in the central nervous system. Specifically, the mechanism limits synaptic breakdown and protein aggregation — major drivers of neurodegeneration.

Praetego’s lead candidate, PTG-630, has demonstrated neuroprotection in multiple preclinical models, including AD, diabetic peripheral neuropathy (DPN), and diabetic retinopathy. In a well-established animal model of Alzheimer’s disease (TG2576), PTG-630 demonstrated the ability to reverse neurodegenerative decline in multiple indices.

The clinical potential of the Amadorin mechanism is substantiated with efficacy data in a disease associated with aging. The pharmacological action of the Amadorins does not involve binding to any specific receptor or enzyme. Rather, they circulate in plasma and rapidly diffuse into tissues, including crossing the blood-brain barrier. This broad-acting protection could allow an Amadorin to serve as a primary disease-modifying drug or as an adjuvant therapy.

Company Milestones

Scientific and Clinical

2020: Intellectual property (IP) claim filed for Amadorins (pharmaceutical composition and claims)
2021: PTG-630 shows efficacy in animal model of DPN and diabetic mild cognitive impairment
2022: PTG-630 shows efficacy in animal model of protection against AD (tau)
2022: IP expansion for novel Amadorins (mechanism of use)
2023: PTG-630 shows reversal efficacy in animal model of AD reversal (tau)
2023: PTG-630 shows reversal efficacy in transgenic mouse models of AD reversal (Ab and tau)
2023: PTG-630 shows efficacy in animal model of diabetic retinopathy
2024: PTG-630 to show reversal efficacy in multiple models of AD
2024: PTG-630 to demonstrate morphological and functional benefit in induced pluripotent stem cells (IPSCs) of AD and high-glucose IPSCs
2024: PTG-630 to demonstrate target engagement in animal brains from AD models where protection and reversal efficacy were demonstrated

Business

2017: Company founded
2018: Angel and founder funding
2018: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Phase 1 Small Business Innovation Research (SBIR) grant for Amadorins for DPN
2020: Angel funding
2020: NIDDK Phase 2 Small Business Technology Transfer (STTR) grant for Amadorins for DPN
2021: NOSI for Amadorins for AD
2022: NIA Direct to Phase 2 SBIR for Amadorins in AD
2023: National Eye Institute (NEI) Phase I STTR grant for Amadorins for diabetic retinopathy
2023: PTG-630 conducts pre-investigational new drug (IND) meeting with the Division of Neurology at the U.S. Food and Drug Administration; indication is early AD
2024: Close on seed funding ($5 million)
2024: PTG-630 IND-enabling studies and IND filing for AD

Financial Overview

Praetego has raised $7 million since its founding in 2017. Approximately $6 million has come from NIH awards from three unique institutions (NIDDK, NIA, and NEI) to further the Amadorin candidates against age-related diseases. The remainder of the funds have come from founders, angel investors, and state grants. Praetego is raising a $5 million seed round to complete IND enabling and prepare for clinical trials. This activity is estimated to take one year. A Series A round ($26 million) will fund Phases 1 and 2 through proof of mechanism, with a timeline of three to four years. With clinical proof, Praetego intends to secure a partnering/licensing deal.

Intellectual Property

Praetego’s Amadorins were developed in house. Filed patents include a series of Amadorin candidates with pharmaceutical composition, composition of matter, and claims. Patent coverage is expected through at least 2040.

Product Development and Regulatory Strategy

Praetego’s first indication is PTG-630 for early Alzheimer’s disease. A pre-IND meeting was completed in December 2023. An IND is intended for late 2024. A traditional Phase 1 program (single ascending dose/multiple ascending dose) will be followed by a Phase 2 study enriched with a patient population at greater risk for cognitive decline — diabetics with demonstrated mild cognitive impairment and other risk factors for AD. Through this Phase 2 study, Praetego intends to demonstrate both target engagement and proof of mechanism in a patient population at high risk for cognitive decline.

The AD program will be followed by clinical programs for PTG-630 to limit DPN and PTG-630 to limit diabetic retinopathy.

Commercialization Strategy

In 2024, Praetego intends to progress PTG-630 toward release to clinics as an oral therapeutic intervention for early Alzheimer’s disease. As a highly potent candidate with preclinical proof in multiple age-related indications, PTG-630 is an ideal addition to a large company portfolio. Because clinical programs for AD are resource-intensive, Praetego seeks to collaborate with a pharmaceutical partner and has identified several suitable global pharmaceutical companies. Praetego maintains open communication channels and routinely updates them with new data. It is Praetego’s intention to seek a transaction as soon as possible to support clinical proof-of-concept trials.

Company Details

Praetego Inc.

Durham, NC

Industry: Therapeutics

Management Team:

Chief executive officer: Pepper Landon
Chief scientific officer: Raja G. Khalifah, Ph.D.
Chief medical officer: Rachel Schindler, M.D.

Point of Contact:
Pepper Landson
pepper@praetego.com
(919) 237-7969