Our Strategy
Our
Strategy
Whereas others have simply reformulated,
we focus on chemistry — and innovation
Unique TAAP™ and MPAR® technology platforms
Ensysce has developed a game-changing 2-step trypsin activation technology, unique to the pharma industry, and is set to revolutionize the way a wide spectrum of drugs are delivered.
Having been awarded important designations by the FDA designed “Fast-track” and “Breakthrough” to speed up development of key product innovations, Ensysce’s lead technologies are moving toward commercialization. TAAP is on the FDA’s “Fast Track” development pathway, and MPAR was recently awarded “Breakthrough Therapy” (BT) designation, a category reserved for innovative life changing / saving therapies. www.fda.gov/drugs/nda-and-bla-approvals/breakthrough-therapy-approvals
Our proprietary TAAP™ (Trypsin-Activated Abuse Protection) tamper-proof technology ensures that a drug can only be activated or turned on when it is swallowed and comes into contact with the natural digestive enzyme trypsin, found in the small intestine. There is no opportunity for activation by manipulation outside of the body as is often the case with other drugs.
Additionally, Ensysce’s proprietary MPAR® (Multi-Pill Abuse Resistance) technology can turn off the activation when too much TAAP™ medication is taken. This does not affect the effectiveness of MPAR® products when taken as prescribed.
This technology holds the promise of eliminating accidental or deliberate overdose. In recognition of this highly innovative approach, the National Institute on Drug Abuse has supported Ensysce in development of MPAR®.
TAAP™
Received FDA “Fast Track” designation.
Trypsin-Activated Abuse Protection
TAAP™ opioids are designed with a 2-step verification mechanism that can’t be manipulated like Abuse Deterrent Formulations.
Activated only by trypsin,
a digestive enzyme that exists only in the gut. Crushing, inhaling or injecting it won’t cause the opioid to be released faster
Provides 12 hrs+ of pain relief,
which is 30% longer than abuse deterrent formulation, providing true twice-a-day dosing
Our proprietary (TAAP™) technology prevents abuse through a 2-step internal Trypsin-Activation process. Our prodrugs are chemically stable molecules that are activated only when administered orally. Due to the activating enzymes not being present in the blood or saliva, there is no opportunity for activation if injected, chewed or snorted.
Most abuse-deterrent opioid products that are currently marketed or in late-stage clinical development fall short of being fully resistant to abuse. Many of them use “extended-release” (ER) formulations. However, ER formulations are still prone to abuse by crushing, chewing, or extracting and injecting for an immediate release of active opioid to achieve rapid, spiking blood levels and a euphoric rush.
TAAP™ limits most forms of drug abuse including chewing, inhaling, manipulation and injection — and is adaptable to most prescription drugs having the potential for abuse.
MPAR®
Received FDA “Breakthrough Therapy” designation
Multi-Pill Abuse Resistance
Combining TAAP™ with MPAR® protects patients from unintended overdose and misuse.
Ensysce’s Multi-Pill Abuse Resistance (MPAR®) is an overdose protection technology that is unique to the industry. It provides a trypsin inhibitor that limits activation with increasing ingestion of product.
A small amount of activation inhibitor is added to each TAAP™ product and does not affect the opioid release if taken as prescribed.
On the other hand, if a prescription is not taken according to directions, or by accidental overdose, MPAR® provides protection by way of a Trypsin Inhibitor which blocks the activation and release of the opioid, allowing the pills to pass through the body inactivated.
The National Institute on Drug Abuse awarded Ensysce approximately $12 Million to develop MPAR®.
Inhibits Trypsin
when too much TAAP™ opioid is swallowed, preventing full activation and opioid release
Only triggered by overdose,
at prescribed dose activity of trypsin will not be affected by MPAR®
Key Applications
TAAP™ and MPAR® technologies have a wide variety of pharmaceutical applications,
and offer a disruptive solution to the many drug abuse crises that are plaguing society today. TAAP™ chemistry governs the way the drug is delivered, using the body’s own enzymes to activate and release the medicine.
TAAP™ and MPAR® technologies are broadly applicable – especially for medicines to treat pain and other CNS disorders where abuse can be an issue, as well as agents that may require improved oral delivery.
In contrast to the other approaches which alter oral delivery by changing the formulation, TAAP™ chemistry reduces the ability to easily manipulate products.
TAAP™ and MPAR® benefits
TAAP™ can provide improved drug performance. Ensysce’s TAAP™ prodrugs can potentially improve attributes of other FDA-approved drugs, through enhanced bioavailability, controlled duration of action, improved safety, increased solubility and reducing susceptibility to abuse.
MPAR® can switch off the activation of TAAP™ products. MPAR provides another layer of protection and safety to Ensysce’s TAAP™ prodrugs.
Composition-of-matter patent protection. All TAAP™ and MPAR® drug products are protected through Composition-of-matter patent protection. TAAP™ applied to other approved therapies produces new composition of matter and provides a strategy for life cycle management.
505(b)(2) NDA pathway. Ensysce’s TAAP™ drug products may be eligible to be developed through the 505(b)(2) NDA regulatory pathway, where if demonstrated to be bioequivalent to an appropriate approved drug, a 505(b)(2) NDA submission may reduce time to commercialization, saving millions in development.
FDA guidance. Given the growing desire of multiple federal agencies – including the FDA – to transition to more abuse-resistant products, Ensysce’s innovative solutions are set to establish us as a market-leading player and partner in an increasingly competitive landscape.
Clinical
Programs
PF614 : TAAP™
PF614 is our lead abuse-protectant TAAP™ product, designed to treat severe and/or chronic pain.
What is PF614?
Proven Pain Relief
PF614 is an oxycodone-based pain medication that has been chemically modified to be inactive until swallowed where it uses one’s own digestive enzymes to activate and release oxycodone to fight pain. Oxycodone has been used for many years to help manage pain severe enough to require an opioid when other pain treatments do not treat pain well enough or you cannot tolerate them. The Ensysce TAAP™ chemical modification delivers pain-relieving medication in a similar manner as OxyContin but with a number of advantages. The pain relief from PF614 should last about 12 hours per dose and you can take it with or without food.
Flexible Administration
There are several ways you can take PF614 that have been demonstrated in clinical studies. If you have difficulty or dislike swallowing pills, PF614 dissolved in water and taken orally still provides the same long lasting pain relief and abuse deterrent profile.
PF614 has been evaluated in multiple Phase 1, Human Abuse Potential, and Phase 2 clinical efficacy studies to demonstrate active drug release, bio-equivalence, low abuse potential and efficacy/time of onset for pain relief. Now poised to enter Phase 3, PF614 is on track to be Ensysce’s first drug product to be commercialized to treat severe pain.
Our key Phase 1 clinical trial evaluated the safety and pharmacokinetic release of oxycodone from a single dose of PF614. Safety data showed that all evaluated doses of PF614 up to an 80mg OxyContin equivalent are well tolerated with no unexpected safety concerns.
The clinical studies for PF614 demonstrated an extended-release profile for the active oxycodone with a 12 hr half-life. This PK profile will provide a true twice-a-day dosing regimen, contrasting other currently available abuse deterrent oxycodone formulations (ADFs) that don’t last as long.
Our Phase 1b clinical trial evaluated the safety and pharmacokinetic release of oxycodone from twice daily doses of PF614, comparing it to branded OxyContin. PF614 100 mg was also found to be ‘Bioequivalent’ to OxyContin 40 mg in healthy subjects under fasted and fed conditions. This shows PF614 can be a direct substitute for OxyContin
The release of oxycodone from PF614 was identical whether delivered as a solid capsule or dissolved in water, suitable for those who have trouble swallowing.
PF614 delivery of oxycodone is equivalent when taken with or without food.
PF614 was evaluated for ‘Drug Liking’ in a group of recreational drug users, as directed by the FDA for labeling claims. PF614 was found to be ‘Not Liked’ following snorting as compared to equivalent doses of oxycodone. Specifically, recreational users indicated they would not ‘Take Drug Again’ suggesting significant abuse protective properties for PF614
The FDA has granted Fast Track designation for development of PF614 for chronic use against severe pain in recognition of the unmet need in this category.
PF614-MPAR®
PF614-MPAR®, the combination of PF614 with the trypsin inhibitor nafamostat, is an abuse resistant opioid with overdose protection, potentially an industry first.
Overdose Protection: PF614-MPAR® has been evaluated in a Phase 1 clinical study for safety and its pharmacokinetic properties and has been shown to effectively reduce oxycodone release from PF614 if greater than 2 dose units (anticipated to be a maximum prescribed dose) are taken simultaneously.
PF614 delivered at increasing doses (15 to 200 mg; PF614-101 study) (dark blue line) and 1, 2, 3, 5 or 8 PF614-MPAR® 25 mg capsules (dose units) administered simultaneously (teal line). Black oval shows oxycodone release is the same if taken at prescribed dose up to 2 capsules of 25 mg PF614 or PF614-MPAR®. Red oval shows overdose protection if PF614-MPAR® is taken at more than 2 dose units compared to PF614 alone.
NAFAMOSTAT
Nafamostat is a potent protease inhibitor. It has been evaluated in a Phase 1 study following oral delivery for tolerability and pharmacokinetics. Nafamostat was well tolerated at doses of up to 200 mg delivered three times daily. Nafamostat works locally in the gut, is being used in our MPAR® drug products to provide overdose protection, and may have utility as a single agent in other indications against SARS or other gut related viral infections. Future studies of nafamostat as a single agent are planned as well as in combination in the PF614-MPAR® (analgesic + overdose protection) drug product.
Preclinical
Programs
PF8001 / PF8026 : TAAP™ AND MPAR® AMPHETAMINE
PF8001 and PF8026 are extended and immediate-release prodrugs of amphetamine for ADHD Medication Abuse utilizing our proprietary TAAP™ and MPAR® technologies.
TAAP™ METHADONE
TAAP-prodrugs for Opioid Use Disorder (OUD) utilizing our proprietary TAAP™ and MPAR® technologies are under development and are moving through preclinical development.
Pipeline
Our pipeline is based on 2 key technologies.
TAAP™ controls how our products are activated and released to improve performance and safety, MPAR® can turn off the activation if too much medication is consumed, thereby protecting from overdose.
Our development pipeline of TAAP™ designed products is led by PF614, a twice daily product for severe and/or chronic pain. TAAP™ has also been applied to other treatments for pain, attention deficit hyperactivity disorder (ADHD) and opioid use disorder (OUD).
Chronic pain affects over 20% of the population and pain is the leading cause of doctor visits worldwide (ref. CDC). Sales of products for chronic and severe pain currently represent a $3.5 Billion dollar market in the US alone* yet current drugs are subject to tampering and abuse that is associated with a significant number of deaths. Ensysce’s TAAP™ and MPAR® technologies are poised to provide the Next Generation of analgesics and disrupt the pain market.
*(ref: IQVIA)
Pain
Oxycodone concentration progression
Unlike OxyContin,
PF614 can’t be chewed, snorted or crushed to release oxycodone inmediately.
PF614: TAAP™ oxycodone
PF614 is our lead product for severe pain based on TAAP™ technology. A follow-on MPAR® combination product is also in clinical development to provide overdose protection. It is our priority program due to larger number of individuals that suffer with severe or chronic pain who are in need of safer therapies. Our technologies will deliver the required efficacy while providing peace of mind of having a safer product in the house.
ADHD
PF8001 / PF8026: TAAP™ amphetamine
PF8001 and PF8026 are extended and immediate-release prodrugs of amphetamine for ADHD utilizing our proprietary TAAP™ technologies. Ensysce designed these TAAP™ prodrugs for use in ADHD in an attempt to improve safety of products for this indication.
OUD – Opioid Use Disorder
Ensysce is continuing to apply its TAAP™ technology for products to treat Opioid Use Disorder (OUD) and is supported by the National Institute for Drug Abuse (NIDA).
Respiratory Diseases
As we have been developing MPAR®, our overdose technology over the past ten years, we have grown a deep knowledge of the protease inhibitor, Nafamostat. We have identified several promising therapies for infectious and respiratory diseases.
Our Partnerships
Delivering Pipeline and Collaboration Opportunites
Strategic collaborations are one of the core components of our business, whether we out-license our TAAP™ and MPAR® technologies to reinvent, revitalize, or develop novel therapies, or we in-license assets for development and commercialization. Ensysce works with their partners to solve their most challenging clinical and business risks. We offer a comprehensive worldwide patent portfolio through our TAAP™ and MPAR® technologies with over 100 issued patents globally. Our industry-leading scientific, regulatory, and commercial expertise offer our collaborators the opportunity to obtain maximum value of their products.
“Ensysce’s prodrug drug delivery solutions can be applied to large component of all current proprietary and generic drugs worldwide” – Dr Lynn Kirkpatrick
OncoZenge AB.
Ensysce entered into a partnership with OncoZenge AB in late 2023 to broaden its portfolio of pain products. OncoZenge, an innovative Swedish company, developed the unique BupiZenge lozenge to treat oral mucositis, a highly painful condition caused by cancer treatments. BupiZenge is to enter Phase 3 studies in Europe, and Ensysce is exploring opportunities to bring BupiZenge through IND enabling studies in the USA. Read more here.
Out-Licensing
Our prodrug technologies can be applied across a broad spectrum of drug therapeutic areas. We can collaborate to deliver novel molecules for clinical development, to revitalize approved medications, and to repurpose approved agents for the benefit of patients and caregivers. Ensysce’s prodrug platform enables new chemical entity (NCE) solutions that allow our collaborators to obtain new patents and extend market positions.
In-Licensing
Ensysce is interested in medicines that are complementary to our existing pipeline in CNS/Pain and will consider products in adjacent therapeutic areas. Our team seeks solutions for rare or complex pain indications and help ensure these medicines become available to the patients who need them.
Beyond Pain – Improved Oral Delivery
Oral route of administration is considered to be the preferred delivery for patients due to convenience, safety, and acceptance. For people suffering from chronic diseases requiring frequent injections, such as diabetes and osteoporosis, an orally delivered drug would be an attractive alternative. Oral delivery is likely to increase compliance, adherence, and improved quality of life.
Ensysce offers both TAAP™ and trypsin inhibitor technology to overcome the challenges of biologic and small molecule delivery.
Why Collaborate with us?
What We Offer
- Our TAAP™ and MPAR® pain and ADHD candidates outside of North America
- Comprehensive global patent portfolio to extend patent and market positions
- Novel prodrug NCEs for generic medicines for product differentiation and market expansion
- Improved GI tract permeation enhancement of peptides and proteins
To Learn More and to Contact Business Development Click Here