REGULATORY PROTEASES UNDERLIE MAJOR INFLAMMATORY AND FIBROTIC DISEASES
Verra transforms the treatment of large unmet medical needs using an innovative small protein platform.
About Us
Verra Therapeutics is a privately held company near Ithaca NY, that was founded in 2017 with a mission of transforming the treatment of certain protease-driven diseases using an innovative small protein platform.
Verra is developing preclinical drug candidates for COPD, Post Heart Attack Recovery and others, by adapting nature’s highly evolved inhibitor sequence for each target.
Dr. Christopher Prince brings decades of leadership experience to the team in managing technology companies through biotech and pharmaceutical development. Dr. Marcia Moss has a comprehensive background in drug discovery and development and is a thought leader on Verra's disease targets.
Verra’s goal is to create novel, selective and impactful drugs for patients with major unsolved medical illnesses.
DRUG TARGETS
Largely membrane-bound, Verra's drug targets lie at the heart of regulatory pathways where localized injury, necrosis, hypoxia, ROS, inflammation and fibrosis are often involved.
Altered activity levels underlie major illnesses with unmet needs:
• lung, kidney and cardiovascular diseases
• autoimmune disorders • fibrosis • cancer
Upregulation in human disease leads to specific inflammatory patterns.
The targets themselves are comprised of multi-domain, multi-functional components with independent roles, thus calling for a delicate approach to intervention.
Selectivity for these targets has been challenging to achieve.
Both historical approaches and the latest trends come up short.
How to Intervene?
Small molecule inhibitors don't work for these drug targets, despite decades and substantial investments, as they lack sufficient surface area for selectivity. They also generally cross the blood brain barrier to raise additional concerns.
Discriminating closely similar target family members is vital to devising a safe and effective drug, as they serve quite different contextual roles.
Antibodies can be selective but are too large, exhibit limited tissue penetration, display sluggish subcutaneous release, and can lead to unintended disruption of target functions on the membrane surface.
Both protein degraders and RNA-based silencing eliminate all domains of these multi-functional and multi-domain proteases, not just the intended activity. Target elimination yields toxic effects and poor performance - and isn't necessary.
A Better Inhibitor Platform
- Based on nature's elegant design for each target, Verra's native peptide sequences meet and exceed the thorny selectivity requirements that small molecules can't.
- VTH144 and VTH245 delicately block only the intended activity, while leaving other complex functions intact.
- They promise better acceptance by the body and reduced immunogenicity.
- Are delivered subcutaneously, with an option for inhaled.
- Much safer than RNAi or protein degraders that eliminate the target.
- Better than antibodies:
- smaller by an order of magnitude, yet with good half life
- bind only to activated targets
- penetrate tissues faster and more fully for better efficacy
- display fast subcutaneous release to the blood
- few antibodies succeed with membrane-bound targets
- Simply manufactured with microbial production.
Pipeline
COPD's THREE Most Deadly Forms
COPD is a debilitating multi-phenotypic disease affecting at least 400 million people worldwide, including 30 million in the US.
Related health care expenses exceed $50 billion annually in major markets. Americans are expected to spend $800 billion over the next 20 years (1).
While phenotypes overlap, the most prevalent forms are Chronic Bronchitis, Emphysema and Small Airway Narrowing.
Sadly, current treatments address primarily symptoms or only a subset of "asthma-like" COPD; there are still no truly disease modifying drugs for most patients and COPD remains an enormous unmet medical need.
1) Elroy Boers, PhD1; Meredith Barrett, PhD2; Jason G. Su, PhD3; et al JAMA Netw Open. 2023;6(12)
A SCOURGE that is MISUNDERSTOOD
- Second only to heart disease for cutting disability-adjusted life span
- Lifetime risk of succumbing is nearly 30% (US)
- The 3rd leading cause of death globally
- An underlying cause of many listed cardiac deaths
- The majority of COPD patients remain to be properly diagnosed.
- Mucus over-production begins at all stages of COPD and increases the risk of all-cause death starting even early-on
What’s new?
A specific protease culprit has been definitively linked with COPD’s three most important phenotypes: emphysema, small airway narrowing and mucus hyper-secretion (chronic bronchitis).
It is up-regulated in the lungs of human patients in proportion to the severity of their disease.
Verra Therapeutics has developed a BEST-IN-Class inhibitor for this target.
Six month gold standard efficacy studies in mice and numerous other studies, demonstrate VTH245’s potential to greatly reduce mucus overproduction and damage in the lung. VTH245 exhibits favorable pharmacokinetics and is compatible with subcutaneous and inhaled routes of administration. Among numerous disease-associated changes, abnormal mucus production, emphysema and harmful elastin degradation are substantially decreased with VTH245.
The drug is very well tolerated in toxicity studies and appears to be suitable for long term chronic use.
ADVANCES IN POST HEART ATTACK RECOVERY WITH VTH144
- Post heart attack therapies are inadequate to address the specific inflammatory and tissue remodeling damage that occurs in modern patients.
- VTH144 is a first and best-in-class drug to thwart both the function loss and the fibrosis which can lead to deadly arrhythmias and heart failure.
- Current drug therapies prevent immediate death, lessen stress on the heart and reduce the likelihood of follow-on heart attacks.
- An avoidable permanent loss of pumping capacity occurs in the post heart attack inflammatory and remodeling phases.
- Heart muscle fibrosis can lead to arrhythmias, heart failure and eventual death in close to 30% of the initially surviving patients.
- Interstitial fibrosis may also frustrate regenerative and device strategies.
- Nothing on the market or in development fully addresses the underlying disease mechanisms in this critical 4-6 week period.
- A newly discovered target is upregulated in the heart muscle of human heart attack patients. It appears to be a key upstream mediating agent.
- VTH144 is a modified native peptide inhibitor sequence that is fully and uniquely selective for this target.
- Cuts heart function losses by more than 3/4 relative to controls (healthy ejection fractions are about 65%).
- And reduces interstitial fibrosis by 2/3.
- VTH144’s performance will not be matched by other approaches.
- Verra seeks to dramatically improve outcomes for heart attack patients and their families.