Phase 3 randomized study to evaluate the safety and efficacy of aprotinin (Trasylol®) administered by inhalation nebulization in patients diagnosed with SARS-CoV-2 (COVID-19) with moderate severity compared to standard therapy. - EFFICACY OF APROTININE IN COVID-19.

Start Date16 Oct 2020

Sponsor / Collaborator-

IRCT20200705048023N1 / SuspendedPhase 3IIT

Evaluation of therapeutic safety and efficacy of tranexamic acid or aprotinin in absolute blood loss and transfusion in pediatric patients undergoing craniosynostosis surgery

Start Date22 Jul 2020

Sponsor / Collaborator

Tehran University of Medical Sciences

100 Clinical Results associated with Aprotinin(Bayer Ag)

100 Translational Medicine associated with Aprotinin(Bayer Ag)

100 Patents (Medical) associated with Aprotinin(Bayer Ag)

6,541

Literatures (Medical) associated with Aprotinin(Bayer Ag)

01 Mar 2024·Tropical animal health and production

Camelina sativa (L. Crantz) products; an alternative feed ingredient for poultry diets with its nutritional and physiological consequences

Review

Author: Ibrahim, Salam ; Hajiazizi, Farzaneh ; Sadeghi, Amirali

Due to increased demand for common feedstuffs such as corn, soybean and fish meals for poultry diets, the search for alternative sources of energy and protein for feed production could help to reduce production costs in the commercial poultry industry. Camelina sativa might be considered a new source of protein, energy and n-3 fatty acids (FA) in poultry diets. The oil content of camelina seeds (CS) is about 35 to 40%. Approximately 50% of this oil is composed of polyunsaturated FA. Moreover, camelina meal (CM) has 16% crude fat. The major n-3 FA of CS and CM is α-linolenic acid (about 30%) which is considered to be nutritionally important. The oil contains other bio-active compounds such as γ-tocopherol, flavonoids and phenolic compounds. Camelina seeds and meal can produce 6258 and 5110 kcal/kg of gross energy, 245-292 and 315-398 g/kg crude protein and 248 and 127 g/kg crude fibre, respectively. However, CS and CM contain 21.77 and 28.08 μmol/g glucosinolates and 12.10 and 12.93 TIU /mg trypsin inhibitors, respectively as anti-nutritional factors (ANFs) that can affect poultry performance adversely. Overall, dietary inclusion of camelina products will supply energy and protein for bird, enhance the antioxidant capacity and lipid stability of poultry products and provide health-promoting n-3 FA and tocopherol rich-foods to humans. However, raw CS contains some ANFs, and its maximum safe level (MSL) is 5% meal or seed, and 2% oil for all type of birds. Hence, it is necessary to establish suitable techniques for removing anti-nutritional factors from CS and increase its MSL in poultry diets.

01 Mar 2024·Analytical biochemistry

Biomolecular characterization of Antheraea mylitta cocoonase: A secreted protease

Article

Author: Pandey, Jay Prakash ; Rani, Aruna ; Pandey, Dev Mani

Cocoonase is a protease secreted during the emergence of silk moths. In the present study cocoonase of Antheraea mylitta was collected, purified and secondary structure was determined using circular dichroism (CD) spectroscopy which revealed the presence of α-helix 4.3%, β-sheet 55%, turn 8% and random coil 32.7%. The thermal stability of cocoonase was studied using CD spectroscopy while the thermal property was observed using Differential Scanning Calorimetry (DSC). Furthermore, MALDI-TOF peptide mass fingerprinting (PMF) was performed for similar protein identification using the MASCOT server. Using casein as the substrate, the kinetic constants Km and Vmax were 13 × 10³ mg/ml and 15.09 × 10^-2 μg/mg.s¹ respectively. The specific activity of cocoonase was observed to be maximum at temperature 40 °C, pH-8.0. The effect of heavy metals Hg²⁺, Cd²⁺, Co²⁺, Pb²⁺ showed inhibitory activity at higher concentrations, while few metals like Mn²⁺, Fe³⁺ enhanced the activity while the effect of Ca²⁺ was not much on the activity. Soybean trypsin inhibitor and PMSF showed an inhibitory effect on the activity of cocoonase. Additionally, antioxidant scavenging and fibrinolytic properties were also observed. Furthermore, the imperative information generated through the present study will serve to explore cocoonase for its prospective pharmaceutical applications.

01 Feb 2024·Current protein & peptide science

Purification, Characterization and Evaluation of the Anticoagulant Effect of an Uncompetitive Trypsin Inhibitor obtained from Bauhinia pulchella (Benth) Seeds

Article

Author: Silva, Romério R S ; Teixeira, Claudener S ; Carneiro, Rômulo F ; Santos, Ana L E ; Santos, Maria H C ; Roma, Renato R ; Dias, Lucas P ; Sampaio, Alexandre H ; Nagano, Celso S ; Silva, Cláudio G L ; Souza, Racquel O S ; Oliva, Maria L V ; Rocha, Bruno A M

Introduction::

Trypsin inhibitors (TIs) have the ability to competitively or non-competitively bind to trypsin and inhibit its action. These inhibitors are commonly found in plants and are used in protease inhibition studies involved in biochemical pathways of pharmacological interest.

Objective::

This work aimed to purify a trypsin inhibitor from Bauhinia pulchella seeds (BpuTI), describing its kinetic mechanism and anticoagulant effect.

Methods::

Affinity chromatography, protein assay, and SDS-PAGE were used to purify the inhibitor. Mass spectrometry, inhibition assays, and enzyme kinetics were used to characterize the inhibitor. In vitro assays were performed to verify its ability to prolong blood clotting time.

Results::

Affinity chromatography on a Trypsin-Sepharose 4B column gave a yield of 43.1. BpuTI has an apparent molecular mass of 20 kDa with glycosylation (1.15%). Protein identification was determined by MS/MS, and BpuTI showed similarity to several Kunitz-type trypsin inhibitors. BpuTI inhibited bovine trypsin as an uncompetitive inhibitor with IC50 (3 x 10-6 M) and Ki (1.05 x 10-6 M). Additionally, BpuTI showed high stability to temperature and pH variations, maintaining its activity up to 100 ºC and in extreme pH ranges. However, the inhibitor was susceptible to reducing agents, such as DTT, which completely abolished its activity. BpuTI showed an anticoagulant effect in vitro at a concentration of 33 μM, prolonging clotting time by 2.6 times.

Conclusion::

Our results suggest that BpuTI can be a biological tool to be used in blood clotting studies.

News (Medical) associated with Aprotinin(Bayer Ag)

13 May 2024

·www.biospace.com

Ensysce Biosciences Reports First Quarter 2024 Financial Results

PF614's Phase 3 Clinical Plans Affirm the Path to Regulatory Approval FDA Breakthrough Therapy Designation of PF614-MPAR Expedites Clinical Program SAN DIEGO, CA / ACCESSWIRE / May 13, 2024 / Ensysce Biosciences Inc. (NASDAQ:ENSC) ("Ensysce" or the "Company"), a clinical stage pharmaceutical company developing innovative solutions for severe pain relief while reducing the potential for opioid abuse and overdose, today reported financial and operational results for the first quarter ended March 31, 2024. Dr. Lynn Kirkpatrick, Chief Executive Officer of Ensysce, commented, "In the first quarter of 2024, we continued to accelerate the progress of our clinical programs toward regulatory approvals. Early in the quarter, a constructive end of Phase 2 meeting was held with the U.S. Food & Drug Administration (FDA) for our lead opioid product, PF614, providing solid guidance for a Phase 3 clinical trial expected to initiate in the second half of 2024. The FDA also provided guidelines to reduce the regulatory risks for our commercialization plan. Additionally, in January, the FDA's grant of Breakthrough Therapy designation for PF614-MPAR affirms belief in our novel approach to providing the ‘Next Generation' of opioid products. This exclusive designation, granted to fewer than 300 drugs since its introduction in 2012, was based on data generated in our Phase 1 study, PF614-MPAR-101, which demonstrated that the unique combination can add oral overdose protection to our prescription TAAP (Trypsin-Activated Abuse Protection) products. This designation is intended to accelerate product development and provide guidance to aid the design of our PF614-MPAR programs to efficiently move toward a new drug application (NDA) submission and approval of this innovative opioid. Coupled with the previously granted Fast Track designation for PF614, Breakthrough Therapy designation for PF614-MPAR demonstrates the FDA's recognition of these transformational pain medications." Dr. Kirkpatrick added, "We look forward to beginning our Phase 3 clinical trials in the second half of 2024. We believe the data we have generated to date from multiple clinical studies de-risk our path to commercialization. These studies have verified PF614 delivers oxycodone in an equivalent manner to commercially available opioids and provides pain relief with reduced abuse potential. We believe our TAAP and MPAR (Multi-Pill Abuse Resistance) opioids have a proven safety pro surpasses the current slate of extended-release opioid analgesics, and we look forward to providing additional milestones and updates in the months ahead," concluded Dr. Kirkpatrick. TAAP TM (Opioid Abuse Deterrent Program) Update Our lead product, PF614, is a Trypsin-Activated Abuse Protection (TAAP TM ) extended-release oxycodone and a potential "next generation" analgesic for severe pain. The Company's TAAP TM technology is designed to control release, be highly resistant to tampering, and reduce abuse through a unique chemical modification. PF614's TAAP TM modification makes it inactive until it is swallowed, following which it is activated or "turned on" to release oxycodone by the body's own trypsin, an enzyme in the small intestine. As mentioned, Ensysce recently received FDA guidance on the strategy and design of its Phase 3 clinical program and expects to commence enrollment for the Phase 3 clinical trial in the second half of 2024. MPAR® (Opioid Abuse Deterrent and Overdose Protection Program) Update PF614-MPAR is a combination product of the TAAP prodrug PF614 with a trypsin inhibitor, designed to treat severe pain while providing overdose protection. MPAR® (Multi-Pill Abuse Resistance) reduces or "turns off" the release of the opioid to prevent an overdose, providing an additional layer of protection to Ensysce's TAAP™ medications. Over the past year, clinical data demonstrated that the MPAR® technology reduces release and absorption of oxycodone from PF614 when consumed in more than a prescribed dose. Ensysce received notice from the FDA that it had granted Breakthrough Therapy designation for PF614-MPAR, specifically acknowledging the potential impact of the innovative MPAR® overdose protection technology. Breakthrough Therapy is an elite designation that expedites the development and review of drugs that are intended to treat a serious condition where the drug may demonstrate substantial improvement over available therapies. In February, the Company received additional productive guidance from the FDA to aid the execution of our PF614-MPAR programs to efficiently move toward a new drug application (NDA) submission and approval to bring this innovative drug to market. Q1 2024 Financial Results Cash - Cash and cash equivalents were $3.4 million as of March 31, 2024, compared to $1.1 million as of December 31, 2023. In January, the Company received cash proceeds of $2.1 million from the exercise of warrants originally issued in the fourth quarter of 2023. Additionally, in February 2024, the Company received gross proceeds of $4.7 million, prior to deducting placement agent fees and offering expenses, from the exercise of warrants originally issued in May 2023. Federal Grants - Funding under federal grants totaled to $0.3 million for the first quarter of 2024 compared to $0.8 million in the comparable year ago quarter. The difference is due to the completion of funding under the MPAR grant in December 2023. Research & Development Expenses - R&D expenses were $0.8 million for the first quarter of 2024 compared to $1.8 million for the same period in 2023. The decrease of $1.0 million was primarily due to reduced external research and development costs related to pre-clinical programs for PF614 and PF614-MPAR. General & Administrative Expenses - G&A expenses were $1.4 million in the first quarter of 2024 compared to $1.6 million for the same period of 2023. The decrease of $0.2 million was primarily a result of reduced stock-based compensation and consulting fees in the 2024 period. Other Income (Expense) - Total other income (expense), net was an expense of $1.3 million for the first quarter of 2024 compared to income of $0.4 million for the same period of 2023. The changes in other expenses were primarily due to interest expense related to convertible notes and non-cash fair value adjustments for convertible notes and warrants. Net Loss - Net loss attributable to common stockholders for the first quarter of 2024 was $3.1 million compared to $2.2 million for the first quarter of 2023. As a clinical stage biotech company, our continued research and development efforts toward regulatory approvals for our product candidates are expected to result in losses for the foreseeable future. About Ensysce Biosciences Ensysce Biosciences is a clinical-stage company using its proprietary technology platforms to develop safer prescription drugs. Leveraging its Trypsin-Activated Abuse Protection (TAAP™) and Multi-Pill Abuse Resistance (MPAR®) platforms, the Company is developing unique, tamper-proof treatment options for pain that minimize the risk of both drug abuse and overdose. Ensysce's products are anticipated to provide safer options to treat patients suffering from severe pain and assist in preventing deaths caused by medication abuse. The platforms are covered by an extensive worldwide intellectual property portfolio for a wide array of prescription drug compositions. For more information, please visit . Definitions TAAP: trypsin activated abuse protection - designed to protect against prescription drug abuse. MPAR: multi-pill abuse resistance - designed to protect against abuse and accidental overdose. Forward-Looking Statements Statements contained in this press release that are not purely historical may be deemed to be forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. Without limiting the foregoing, the use of words such as "may," "intends," "can," "might," "will," "expect," "plan," "possible," "believe" and other similar expressions are intended to identify forward-looking statements. The product candidates discussed are in clinic and not approved and there can be no assurance that the clinical programs will be successful in demonstrating safety and/or efficacy, that Ensysce will not encounter problems or delays in clinical development, or that any product candidate will ever receive regulatory approval or be successfully commercialized. All forward-looking statements are based on estimates and assumptions by Ensysce's management that, although Ensysce believes to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Ensysce expected. In addition, Ensysce's business is subject to additional risks and uncertainties, including among others, possible NASDAQ delisting, the initiation and conduct of preclinical studies and clinical trials; the timing and availability of data from preclinical studies and clinical trials; expectations for regulatory submissions and approvals; potential safety concerns related to, or efficacy of, Ensysce's product candidates; the availability or commercial potential of product candidates; the ability of Ensysce to fund its continued operations, including its planned clinical trials; the dilutive effect of stock issuances from our fundraising; and Ensysce's and its partners' ability to perform under their license, collaboration and manufacturing arrangements. These statements are also subject to a number of material risks and uncertainties that are described in Ensysce's most recent annual report on Form 10-K and current reports on Form 8-K, which are available, free of charge, at the SEC's website at Any forward-looking statement speaks only as of the date on which it was made. Ensysce undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required under applicable law. Ensysce Biosciences Company Contact: Lynn Kirkpatrick, Ph.D. Chief Executive Officer (858) 263-4196 Ensysce Biosciences Investor Relations Contact: Shannon Devine MZ North America Main: 203-741-8811 ENSC@mzgroup.us Ensysce Biosciences, Inc. Condensed Consolidated Statements of Operations (Unaudited) Three Months Ended March 31, 2024 2023 Federal grants $ 305,722 $ 789,635 Operating expenses: Research and development 778,904 1,796,015 General and administrative 1,369,782 1,554,855 Total operating expenses 2,148,686 3,350,870 Loss from operations (1,842,964 ) (2,561,235 ) Total other income (expense), net (1,273,599 ) 369,429 Net loss $ (3,116,563 ) $ (2,191,806 ) Adjustments to net loss (216 ) (4,368 ) Net loss attributable to common stockholders $ (3,116,779 ) $ (2,196,174 ) Net loss per share attributable to common stockholders, basic and diluted $ (0.55 ) $ (2.08 ) Ensysce Biosciences, Inc. Condensed Consolidated Statements of Cash Flows (Unaudited) Three Months Ended March 31, 2024 2023 Net cash used in operating activities $ (3,408,403 ) $ (3,606,919 ) Net cash provided by financing activities 5,689,148 1,874,982 Change in cash and cash equivalents 2,280,745 (1,731,937 ) Cash and cash equivalents at beginning of period 1,123,604 3,147,702 Cash and cash equivalents at end of period $ 3,404,349 $ 1,415,765 Ensysce Biosciences, Inc. Condensed Consolidated Balance Sheets (Unaudited) March 31, December 31, 2024 2023 Assets Current assets: Cash and cash equivalents $ 3,404,349 $ 1,123,604 Prepaid expenses and other current assets 1,292,291 1,165,264 Total current assets 4,696,640 2,288,868 Other assets 377,550 419,217 Total assets $ 5,074,190 $ 2,708,085 Liabilities and stockholders' equity (deficit) Current liabilities: Accounts payable $ 981,720 $ 1,936,007 Accrued expenses and other liabilities 408,435 542,260 Notes payable and accrued interest 245,973 854,697 Total current liabilities 1,636,128 3,332,964 Long-term liabilities 17,433 26,388 Total liabilities 1,653,561 3,359,352 Stockholders' equity (deficit) 3,420,629 (651,267 ) Total liabilities and stockholders' equity (deficit) $ 5,074,190 $ 2,708,085 SOURCE: Ensysce Biosciences, Inc. View the original press release on accesswire.com

Financial StatementPhase 1Fast TrackBreakthrough TherapyPhase 3

28 Aug 2023

·www.biospace.com

Promising Vertex Pain Med Points to New Era for Analgesics

Pictured: An illustration of a woman overlooking a field with pill-shaped sheep/Nicole Bean for BioSpace† A medication called VX-548, developed by Vertex Pharmaceuticals, proved superior to placebo in two small Phase II clinical trials for two types of post-surgical pain, according to a study published in The New England Journal of Medicine in early August. Though the effect was modest, “these trials represent an early foray into an exciting new class of drugs in a difficult field,” Mark Wallace, a physician at UC San Diego’s division of pain medicine who was not involved in the research, wrote in an accompanying editorial. The medication heads now to two Phase III trials with 1,000 participants each, plus an open-label study with 250 participants. The results couldn’t come at a better time, as the opioid epidemic continues to ravage the U.S., with 50,000 people dying each year from overdose, and 10 million abusing the highly addictive medications annually. The U.S. Department of Health and Human Services (HHS) officially declared opioid abuse a public health emergency in 2017, but until there is a safe and effective alternative to opioids, acute and chronic pain present a silent scourge of their own. “There is an immense unmet need for new pain medications, even without the opioid epidemic,” Stephen Waxman, a Yale neuroscientist who penned another editorial accompanying the recent NEJM study, told BioSpace. At least one other firm is pursuing the same target as Vertex, while others are exploring different pain-blocking approaches. “There hasn’t been a new class of pain medicine in more than 20 years,” Vertex spokesperson Heather Nichols told BioSpace in an email. “We believe we could redefine the treatment of pain with the first new mechanism of action in decades.” Meanwhile, other companies are looking to make opioids themselves safer by removing their addictive qualities. Vertex Therapeutic Helps Quell Acute Pain Vertex researchers zeroed in on two distinct, repeatable sources of pain: bunionectomy (a type of foot surgery) and abdominoplasty (tummy tuck), both of which necessitate analgesic medication for acute, post-operative pain. The design allowed for a homogenous patient population, where specific pain was triggered by the same injury. A total of 274 participants were enrolled in the bunionectomy trial, and 303 participants in the abdominoplasty trial. Participants rated their pain at 19 time points on a scale of zero (no pain) to 10 (the worst pain one can imagine). This led to an overall score known as sum of the pain-intensity difference, or SPID, a measurement the FDA recommends as a primary endpoint in acute pain trials. Though a moderate dose of VX-548 did not show a significant improvement over placebo, a high dose did. In fact, the high dose acted rapidly, within the first hour of treatment. At 48 hours, the high dose offered more patients at least a 30% reduction in the score on the pain rating scale than placebo did. Side effects such as nausea, headaches or constipation were mild or moderate, and temporary. Participants on the high dose were less likely to stop medication early because they felt it wasn’t helping than patients on placebo or given a common painkiller that combines hydrodocone bitartrate and acetaminophen. The new molecule is the end result of decades of research into peripheral voltage-gated sodium channels, often referred to as NaV channels, which are found in sensory neurons outside the brain and are responsible for detecting painful or noxious stimuli. There are nine different types of voltage-gated sodium channels in the body (NaV1.1 to NaV1.9); Vertex’s new medication targets NaV1.8, which is expressed exclusively in sensory neurons of the peripheral nervous system and not the brain. Researchers have raised concerns about the results, including the fact that the trials were small, and that a higher (thus more effective) dose of acetaminophen/oxycodone was not tested. Nonetheless, Waxman, whose work on peripheral voltage-gated sodium channels has been widely published, pointed out that the study was a proof-of-concept trial. “It wasn’t necessarily a home run,” he told BioSpace, “but it showed that blocking peripheral gated sodium channels does reduce pain, without central nervous system side effects and without addictive potential.” Waxman added that he is hopeful that these findings will eventually lead to broadly effective treatments for chronic pain as well. Vertex is already conducting a Phase II trial on diabetic neuropathy, with a study completion date in spring of 2024. Other Approaches in Development for Pain Management Vertex is not alone in its quest. “It’s been a race for the holy grail,” commented Waxman. “In 2006, we established very clearly that NaV1.8 is a major controller of the repetitive firing of pain signaling in neurons and if you could block it you would reduce pain.” In Finland, Orion Pharmaceuticals is working on developing a non-opioid pain therapy dubbed JMKX000623 that also blocks the NaV1.8 sodium channel. This experimental therapy is in Phase I trials. And here in the U.S., Virpax Pharmaceuticals is looking at other pain targets and approaches. One of its new analgesics is a liposomal, long-acting, injectable formulation of bupivacaine, a potent local anesthetic similar to lidocaine. It is intended for post-operative pain management and Virpax is developing the formulation in conjunction with the U.S. Army, which is studying its potential in battlefield wounds. The company is also planning Phase I safety trials on two intranasal sprays that would target pain centers in the brain—one is a peptide called enkephalin, and the other, a pharamaceutical-grade cannabidiol. Meanwhile, in an entirely different approach, biotech startup Ensysce Biosciences has developed a novel chemistry that modifies how opioids are released when taken in order to make them safer. The platform, called TAAP (trypsin activated abuse protection), uses the body’s own digestive enzyme, trypsin, to trigger release of the opioid. That means the pills won’t work if they crushed in order to be snorted or injected—the kind of recreational abuse that is common. The opioid can only be activated in the stomach in the presence of trypsin. In addition, overdose protection is ensured by adding a tiny amount of trypsin inhibitor to every dose. “If you take the prescribed amount, the amount of trypsin inhibitor is negligible so nothing happens,” explained chemist Lynn Kirkpatrick, CEO at Ensysce Biosciences. “But if you take more than you should, there is enough inhibitor to shut down the activation.” The company’s molecule is called PF614 and is currently in Phase II clinical trials, and fast tracked by the FDA. It is a prodrug of oxycodone, with a safety pro to other traditional opioids, but a 12-hour half-life once ingested, which is longer-acting than current opioids. “We are talking to the FDA about Phase III plans,” Kirkpatrick told BioSpace. If all goes as planned, she said, the company might have an NDA submitted to the agency by 2025. Jill Neimark is a freelance science writer based in Macon, Georgia. Reach her at jillneimark.com.

Phase 2Clinical ResultPhase 3

30 May 2023

·www.biospace.com

Opinion: What to Expect From an Experimental Anti-Abuse Opioid Drug

Pictured: Loaded syringe and opioids/iStock, Darwin Brandis In recent years, oxycodone has accrued a murky reputation. When first introduced as OxyContin in 1996 by Purdue Pharma, the opioid was heavily marketed as a miracle painkiller. However, with side effects such as euphoria, oxycodone has also become a highly sought substance among drug addicts. In addition, the risk of overdose is ever-present, with death likely if too much oxycodone is consumed at once. Oxycodone currently comes in various oral formulations such as tablets, capsules and oral solutions. These formulations can be abused by crushing them into a powder that can be inhaled or injected for a more immediate and potent euphoric effect, and opioid addiction continues to be a major problem nationwide. According to the National Institutes of Health, drug overdose deaths involving prescription opioids totaled 16,706 in 2021 in the U.S., while the total number of opioid-related deaths, prescription or otherwise, was 80,411. While past players in the opioid space, such as Purdue, have faced lawsuits for pushing opioids to the unsuspecting public, pharmaceutical manufacturers have begun attempting to stem abuse—by, for example, developing extended-release oral oxycodone formulations. However, studies have demonstrated that even these formulations can be modified for euphoric effects and therefore continue to be abused. But there is one company with a product that, while early stage, appears promising in effectively combatting opioid addiction and overdose. Ensysce’s Abuse-Resistant Tech Ensysce Biosciences is looking for answers to resolve the prescription drug abuse epidemic. In the pain space, Ensysce is developing its Trypsin-Activated Abuse Protection (TAAP) tamper-proof technology, which can prevent oxycodone and other opioids from working until the drug reaches the small intestine, where the abundance of trypsin will activate the opioid. Because the opioid requires the presence of trypsin to become active, TAAP ensures the formulation will not lead to euphoria if crushed and snorted or injected. In addition, the company is using a trypsin inhibitor called nafamostat to limit activation with increasing ingestion of the product, thereby setting a maximum limit to the overall effect that can be derived from the drug and protecting against overdose. In results released in January 2023, Ensysce showed that its Multi-Pill Abuse Resistance technology, along with TAAP in its oxycodone capsule formulation (PF614-MPAR), has safety features that can reduce the emergence of habit-forming behaviors compared to regular oxycodone. And in May 2023, Phase I results demonstrated the effectiveness of the second prong of the technology: when three or more capsules were consumed simultaneously, the drug elicited a maximal response and drug levels even decreased compared to the unprotected PF614 formulation. Although Ensysce is currently recruiting for more pharmacokinetic trials, there is still a long way to go on the pain front. Phase II and III trials have not yet commenced, so while efficacy is assumed based on previous studies performed by others related to oxycodone as an active ingredient, the efficacy of this formulation has not yet been proven in pain patients. Therefore, Ensysce’s pain products may not hit the market until the latter half of this decade at the earliest. In addition, given that the pancreas manufactures trypsinogen before the substance enters the small intestine and is converted to trypsin, it is likely that patients will need to have a healthy, functioning pancreas for optimal effect. Nonetheless, Ensysce’s technology is the most promising seen to date for confronting addiction with a preventative formulation. The company is also working on anti-abuse formulations of other substances, such as amphetamine (used to treat ADHD), though these programs are in preclinical stages. Therefore, keep an eye on Ensysce as its pipeline results start to emerge. Jia Jie Chen writes analyses focusing on drug development in the biotech and pharma industries for BioSpace. He has a doctorate degree in pharmacy and experiences ranging from biotech equity research to business intelligence analysis. Follow him on LinkedIn.

Clinical ResultPhase 1Phase 2

100 Deals associated with Aprotinin(Bayer Ag)

External Link

KEGG	Wiki	ATC	Drug Bank
D02971	Aprotinin(Bayer Ag)	B02AB01	DB06692

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hemorrhage	US	Bayer HealthCare Pharmaceuticals, Inc.	29 Dec 1993

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Esophageal Carcinoma	Phase 3	US	Bayer AG	01 Dec 2005
Esophageal Carcinoma	Phase 3	AU	Bayer AG	01 Dec 2005
Esophageal Carcinoma	Phase 3	AT	Bayer AG	01 Dec 2005
Esophageal Carcinoma	Phase 3	BE	Bayer AG	01 Dec 2005
Esophageal Carcinoma	Phase 3	CA	Bayer AG	01 Dec 2005
Esophageal Carcinoma	Phase 3	DK	Bayer AG	01 Dec 2005
Esophageal Carcinoma	Phase 3	FR	Bayer AG	01 Dec 2005
Esophageal Carcinoma	Phase 3	DE	Bayer AG	01 Dec 2005
Esophageal Carcinoma	Phase 3	ES	Bayer AG	01 Dec 2005
Esophageal Carcinoma	Phase 3	GB	Bayer AG	01 Dec 2005

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ART (Arterial Revascularization Trial) (Pubmed \| J Am Heart Assoc)	Not Applicable	complication of coronary artery bypass graft	3,102	Aprotinin	ktggjiukia(vnfdwncqpp) = ylczearnqw aoaabcbfde (hbfvueyqli ) View more	Negative	03 Mar 2018
ARVO2009	Not Applicable	Uveitis	-	Aprotinin	jxgmilagac(qdojpahtdg) = uxnctfcetp dkxfezakis (jklseoavvn ) View more	-	01 Apr 2009
Pubmed \| Eur J Cardiothorac Surg	Not Applicable	-	112	Aprotinin	vmrlynteyc(kijkxnethn) = eehdycriir lynjbeoeol (ovhvmurtsp )	-	01 Feb 2006
				Aprotinin	vmrlynteyc(kijkxnethn) = iywausjuag lynjbeoeol (ovhvmurtsp )
Pubmed \| Can J Anaesth	Not Applicable	postoperative cognitive dysfunction	-	Aprotinin	vwszueblbm(teqhpijhji) = neuircayus iwmzcvvznj (hytvmpssrk )	-	01 Dec 2004
				Placebo	vwszueblbm(teqhpijhji) = thikhnxltw iwmzcvvznj (hytvmpssrk )
ARVO2004	Not Applicable	uPA \| tPA	-	Aprotinin treatment	uatjnvpaut(uvbjeqdhss) = plasminogen-dependent casein hydrolysis was restricted to the leading edge of migrating epithelial cells in no-aprotinin and aprotinin treated corneal tissue after PRK. The hydrolysis was inhibited by a polyclonal anti-uPA antibody, amiloride, but not with polyclonal anti-tPA antibody. No plasminogen-independent lysis was observed. gnuojzdmfa (omdzyyjhhx ) View more	-	01 May 2004
				No Aprotinin treatment

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