Periodic Reporting for period 1 - PANNEXIN (Pannexin 1 – a novel target for pediatric orphan epilepsy)
Période du rapport: 2023-10-01 au 2024-09-30
Panntherapi is a pharmaceutical company developing innovative drugs in Neurology. Our goal is to promote higher efficient products and to improve quality of life of patients.
We are first focusing on epilepsy. Epilepsy is the first neurological condition of children, the third of adults, and concerns around 1% of the general population. Epilepsy is defined by recurrent seizures and there are multiple types of epileptic syndromes. Currently around 30% of epileptic patients do not still respond to any anti-seizure drugs and it can grow up to more than 70% in some epileptic syndromes. When it is possible, some patients undergo a surgery to remove the part of the brain involved in the genesis of the seizures, but it fails to be effective in several cases.
Two top notch scientists, both ERC Consolidators and scientists at “Paris Sciences et Lettres” University, got the opportunity to obtain some post-operative brain tissues from epileptic patients. Using this ex vivo tissues, they demonstrated that the tissues continue to have some seizures, allowing to study the pathophysiology of the disease. They identified the interest of a new channel, overexpressed only in pathological tissues, and involved in the genesis of seizures. They demonstrated that blocking this channel allow to fully stop the seizures in more than 80% of the cases using the post operative brain tissues of epileptic patients but also in a representative preclinical model of resistant epilepsy. And the blockage of the channel seems to have no impact on other cognitive functions.
And following the publication of our scientists, the involvement of this channel was demonstrated in the genesis of crisis of other chronic neurological diseases such as multiple sclerosis, pain, etc.
Panntherapi was founded based on this innovation: to develop more efficient and safer drugs for patients.
Our first product is indicated in a highly resistant rare paediatric epilepsy where more than 70% of patients have currently no solution. This indication was identified based on results from ex vivo post-operative brain tissues’ studies where tissues from those patients among others were successfully tested with the identified drug candidate able to block the channels. Panntherapi has developed a long-release paediatric formulation adapted to children from 6 months of age.
The goal of the EIC accelerator program is to support the clinical development of our candidate in epilepsy: first study in healthy volunteer allowing to demonstrate the safety and the long release profile of the product, and then a first study in patients allowing to evaluate the efficient dose and the safety.
We expect to give access of our product to patients first by a compassionate use program in 2027 and to then pursue the development up to final registration and market access. In parallel, Panntherapi is also developing new candidates acting on the same target to be indicated in other chronic neurological diseases with crisis.
We are first focusing on epilepsy. Epilepsy is the first neurological condition of children, the third of adults, and concerns around 1% of the general population. Epilepsy is defined by recurrent seizures and there are multiple types of epileptic syndromes. Currently around 30% of epileptic patients do not still respond to any anti-seizure drugs and it can grow up to more than 70% in some epileptic syndromes. When it is possible, some patients undergo a surgery to remove the part of the brain involved in the genesis of the seizures, but it fails to be effective in several cases.
Two top notch scientists, both ERC Consolidators and scientists at “Paris Sciences et Lettres” University, got the opportunity to obtain some post-operative brain tissues from epileptic patients. Using this ex vivo tissues, they demonstrated that the tissues continue to have some seizures, allowing to study the pathophysiology of the disease. They identified the interest of a new channel, overexpressed only in pathological tissues, and involved in the genesis of seizures. They demonstrated that blocking this channel allow to fully stop the seizures in more than 80% of the cases using the post operative brain tissues of epileptic patients but also in a representative preclinical model of resistant epilepsy. And the blockage of the channel seems to have no impact on other cognitive functions.
And following the publication of our scientists, the involvement of this channel was demonstrated in the genesis of crisis of other chronic neurological diseases such as multiple sclerosis, pain, etc.
Panntherapi was founded based on this innovation: to develop more efficient and safer drugs for patients.
Our first product is indicated in a highly resistant rare paediatric epilepsy where more than 70% of patients have currently no solution. This indication was identified based on results from ex vivo post-operative brain tissues’ studies where tissues from those patients among others were successfully tested with the identified drug candidate able to block the channels. Panntherapi has developed a long-release paediatric formulation adapted to children from 6 months of age.
The goal of the EIC accelerator program is to support the clinical development of our candidate in epilepsy: first study in healthy volunteer allowing to demonstrate the safety and the long release profile of the product, and then a first study in patients allowing to evaluate the efficient dose and the safety.
We expect to give access of our product to patients first by a compassionate use program in 2027 and to then pursue the development up to final registration and market access. In parallel, Panntherapi is also developing new candidates acting on the same target to be indicated in other chronic neurological diseases with crisis.
Two major deliverables were due during the first reporting period.
Deliverable D1.1. & Milestone 1: Result of the Phase 1 Clinical study
The goal of the Phase 1 clinical trial is to evaluate in healthy adult volunteers the long-release profile and the safety of our PTI5803 product.
Indeed, preliminary to the start of the Phase I study, Panntherapi has developed a prolonged release formulation for PTI5803. This new formulation was developed with our subcontractor Recipharm. Several options were evaluated according to their PK profile in vitro and in vivo (large animal studies) as well as their stability over time. The final formulation and associated manufacturing process has been selected by the end of 2023.
Study set-up
The regulatory documentation for the Phase I study was submitted in March 2024 to the Ethics committee and the ANSM (Agence National de Sécurité du Médicament Français). In parallel, a first clinical batch have been manufactured for the execution of the clinical phase 1.
Feedback from ethical and regulatory authorities were received in May and June 2024. The final approval was received on July 6th, 2024.
Execution of the Phase 1 clinical trial and results
The Phase 1 clinical trial is performed in France in a single investigation centre at Optimed. The site initiation visit was performed on July 16th, allowing to start inclusion of subjects at that time.
The Phase I study is on track but had some delays and the final study report will be available in 2025.
Deliverable D2.1: PIP (Paediatric Investigation Plan) Submission:
The objective of the paediatric Investigational Plan is to validate the development program with the European regulatory medical agency, EMA, in regard of paediatric specificities before starting the clinical trials in patients (even in adult). It is a regulatory requirement which can impact the Market Access Approval if it was not performed in due time.
Key Opinion Leaders meetings
In November 2023, Panntherapi performed a meeting with European clinicians and regulatory experts to discuss the development plan, the synopses of the different clinical trials in patients and the related regulatory strategy. The objective of this meeting was also to construct the questions to be asked to EMA during a scientific advice.
Scientific advice
Based on the exchanges during the KOL meeting and in agreement with scientific, operational and management discussion, Panntherapi has prepared the document to perform a Scientific Advice with EMA.
The official feedback received from the Agency in May provide very positive feedback with very constructive input for the future development of PTI5803
The Agency strongly advise for follow up Scientific Advice to be sought whenever we generate appropriate new data.
Paediatric Investigational Plan
Following the comments from the SWAP committee, our development plan was updated and propose to the PDCO (paediatric committee), submitting the Paediatric Investigation Plan on June 3rd for a procedure start on July 8th, 2024.
We will receive the final comments by end of September 2024.
Deliverable D1.1. & Milestone 1: Result of the Phase 1 Clinical study
The goal of the Phase 1 clinical trial is to evaluate in healthy adult volunteers the long-release profile and the safety of our PTI5803 product.
Indeed, preliminary to the start of the Phase I study, Panntherapi has developed a prolonged release formulation for PTI5803. This new formulation was developed with our subcontractor Recipharm. Several options were evaluated according to their PK profile in vitro and in vivo (large animal studies) as well as their stability over time. The final formulation and associated manufacturing process has been selected by the end of 2023.
Study set-up
The regulatory documentation for the Phase I study was submitted in March 2024 to the Ethics committee and the ANSM (Agence National de Sécurité du Médicament Français). In parallel, a first clinical batch have been manufactured for the execution of the clinical phase 1.
Feedback from ethical and regulatory authorities were received in May and June 2024. The final approval was received on July 6th, 2024.
Execution of the Phase 1 clinical trial and results
The Phase 1 clinical trial is performed in France in a single investigation centre at Optimed. The site initiation visit was performed on July 16th, allowing to start inclusion of subjects at that time.
The Phase I study is on track but had some delays and the final study report will be available in 2025.
Deliverable D2.1: PIP (Paediatric Investigation Plan) Submission:
The objective of the paediatric Investigational Plan is to validate the development program with the European regulatory medical agency, EMA, in regard of paediatric specificities before starting the clinical trials in patients (even in adult). It is a regulatory requirement which can impact the Market Access Approval if it was not performed in due time.
Key Opinion Leaders meetings
In November 2023, Panntherapi performed a meeting with European clinicians and regulatory experts to discuss the development plan, the synopses of the different clinical trials in patients and the related regulatory strategy. The objective of this meeting was also to construct the questions to be asked to EMA during a scientific advice.
Scientific advice
Based on the exchanges during the KOL meeting and in agreement with scientific, operational and management discussion, Panntherapi has prepared the document to perform a Scientific Advice with EMA.
The official feedback received from the Agency in May provide very positive feedback with very constructive input for the future development of PTI5803
The Agency strongly advise for follow up Scientific Advice to be sought whenever we generate appropriate new data.
Paediatric Investigational Plan
Following the comments from the SWAP committee, our development plan was updated and propose to the PDCO (paediatric committee), submitting the Paediatric Investigation Plan on June 3rd for a procedure start on July 8th, 2024.
We will receive the final comments by end of September 2024.
Validation of the formulation
The development of the long-release paediatric formulation allows to file a patent in August 2023 .
Phase 1 clinical trial
The phase 1 clinical results will allow to implement the PK/PD and PBPK modelling and to update accordingly the Phase 2 clinical protocol (choice of the tested doses). No further research is needed a priori (to be reevaluated based on Phase 1 results).
Regulatory exchanges
Feed-back from EMA following the Scientific Advice and the Paediatric Investigational Plan, allowed us update and execute accordingly our development plan.
The development of the long-release paediatric formulation allows to file a patent in August 2023 .
Phase 1 clinical trial
The phase 1 clinical results will allow to implement the PK/PD and PBPK modelling and to update accordingly the Phase 2 clinical protocol (choice of the tested doses). No further research is needed a priori (to be reevaluated based on Phase 1 results).
Regulatory exchanges
Feed-back from EMA following the Scientific Advice and the Paediatric Investigational Plan, allowed us update and execute accordingly our development plan.