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KDDF-201512-08 Phase 2A Clinical Study of JPI-289 for the Treatment of Stroke(CNS Diseases, Chemical) [2019-05-27]

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Ongoing Project
Section Lead
Generation
Lead
Optimization
Preclinical Phase I Phase II Phase III

Development and Market Objectives

The aim of this project is to accomplish phase 2A clinical trial in acute ischemic stroke patients including evaluation of efficacy, PK/PD profiles, and safety/ tolerability of JPI-289 with low and high doses, and to proceed phase 2B clinical development of the PARP-1 inhibitor, as a first-in-class drug for the treatment of stroke.


Ultimately, after rapid completion of the Proof of Concept (POC, Phase 2A) clinical studies, Jeil Pharmaceutical is planning to license out, co-develop, and co-commercialize JPI-289 with global big companies.

Unmet Medical Need & Target Patients

Stroke is a debilitating condition, with the highest death rate as a single organ disease. Incidence is expected to keep increasing over the next 20 years despite the progress in modern medical science and technology. This is largely due to a global increase in the aging population.


No clinically effective therapies currently exist although the stroke incident rate in Korea remains high. Developments of new therapeutic strategies and standards of medical care are imperative. 


Currently, treatment for ischemic stroke with cerebral blood vessel occlusion predominantly employs a thrombolytic agent combined with surgery, and further agents including anticoagulants and platelet aggregation inhibitors for secondary prevention. Any new therapy for stroke is expected to be highly marketable, as the only thrombolytic agent, tPA (tissue Plasminogen Activator) has been approved by the FDA with limitations so far.


Jeil Pharmaceutical will develop JPI-289, a PARP-1 inhibitor, on a commercial scale after acquiring Proof-of-Concept data via a combination therapy with tPA and/or thrombectomy in Phase 2A clinical trials. This will be followed by licensing-out and co-development with multinational partners.


A homogeneous patient group will be selected for a combination therapy with tPA and/or thrombectomy for NDA approval, with the range of subjects and indications further expanded through PMS clinical trials.

Status

A clinical protocol for a phase 2A clinical trial of JPI-289 was approved by Ministry of Food and Drug Safety (MFDS) and review by Institutional Review Boards (IRBs) of 8 Clinical Research Centers including Seoul National University Hospital is currently in progress. 


Administration and interim analyses for cohort 1, 2 will be performed in 2016, and based on the results, a dose for cohort 3 will be determined. Administration and analysis for cohort 3 will be started in 2017. 


A protocol for a phase 2B clinical trial in stroke patients will be developed by   early 2018. After acquiring IND/IRB approvals for the phase 2B clinical trial of JPI-289, Jeil Pharmaceutical will enter phase 2B clinical trial during the second half of 2018.

Intellectual Property

Patent applications covering materials and preparation methods were submitted in 2008, and the registration was approved in 2010 in Korea (10-0968175), as well as in the US, Europe, China, Japan, Australia, Canada, Russia, Mexico, and Hong Kong during 2011 and 2015.
- PCT: WO 2010/056038


Application for the JPI-289 crystalline structure patent was submitted in 2012.


In summary, one application in Korea and nine international applications have been registered, and review processes for registration of another application in Korea and six international applications are currently underway.  

Competitive Advantages

The majority of previous stroke candidates have been designed to inhibit apoptosis mechanisms; however, the clinical results have been inconclusive as most of the brain damages were caused by necrosis during the first 10 hours after the stroke occurs. 


JPI-289 inhibits the damages caused by necrosis, apoptosis and inflammation, at the same time, and is expected to exert significant benefits in the treatment of stroke. 

 

 

Competitive advantages
① Inhibition of PARP-1 is a significantly distinct mechanism of action when compared to other candidates and is expected to show high efficacy in clinical trials with ischemic stroke patients through the neuroprotective effects. 
② Effective PARP-1 inhibition and the mechanism of action by MP-124 have been proven in a monkey model, which is the closest stroke primate animal model to human so far. In a monkey tMCAO stroke model, JPI-289 showed 49% decrease in infarction volume, which is the best result in the world when compared with that of 21% decrease in infarction volume by MP-124. Therefore, JPI-289 among PARP inhibitors is considered as one of the most promising agents for the treatment of stroke. 
③ Safety of JPI-289 has been confirmed in healthy volunteers because there were no serious adverse events (SAEs) during phase 1 study. AUCs of JPI-289 in the blood were increased dose-proportionally.
④ JPI-289 is highly soluble with excellent PK parameters. Single doses of JPI-289 significantly decreased infarct volume in an SD rat stroke model. Therefore, it is expected to be suitable for acute ischemic stroke patients who are required a prompt administration and onset of efficacy.
⑤ When JPI-289 was co-administered with tPA in the rat embolic tMCAO models, the infarction volume and hemorrhage area were significantly decreased compared to those of tPA single treatment group.
⑥ Because JPI-289 can be taken as an oral administration due to relatively high bio-availability (rat: 66%, dog: 100%) as well as an injection, treatment of stroke with JPI-289 after discharge is predicted to be maximized.  
⑦ JPI-289 has shown excellent safety profiles in non-clinical studies, leading to IND approval for Phase 1 clinical trials in healthy male subjects. This is in favorable contrast to MP-124, another leading candidate that has been in Phase 1 since 2009. Acquisition of clinical POC via rapid completion of Phase 2A is expected to endow an advantageous position in licensing-out to global big pharmaceutical companies. 
⑧ After secure of clinical POC, the drug value will be maximized by expanding its application for other diseases (e.g. myocardial infarction, Delayed Graft Function, Acute Kidney Injury) and patient groups.
⑨ S100B, NSE will be scrutinized further to develop as a bio-marker of stroke in upcoming studies.
⑩ The synthetic process of JPI-289 has been established with API/DP production in cGMP facilities for Phase 1/2 trials. As a result, mass production for commercial purposes is tangible.
⑪ A huge market value has been established with monopolistic right until 2029.

Contact & Company Overview

Related Project

Related Project
Phase IB Clinical Study of JPI-289 for the Treatment of Stroke Project view
Phase I Clinical Development of JPI-289 for the Treatment of Stroke Project view
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