SynAct Pharma AB (“SynAct Pharma”) today published answers to questions about the further development of AP1189 – a drug candidate for the treatment of acute impairments in chronic inflammatory diseases.
What is the plan for the final Phase I study?
The remainder of the Phase I study (multiple ascending dose) is planned to be conducted using the suspension (collection of the drug in liquid) successfully used in the initial Phase I (single ascending dose) study. The suspension thus replaces the experimental tablet formulation that had been shown to result in too high a degree of variability in plasma concentrations, which would make it difficult to predict the amount of AP1189 in the blood after taking the tablet. SynAct Pharma has therefore decided to continue the development of AP1189 using the suspension instead of the tablet.
Production of the trial material (AP1189 in suspension) has begun and is expected to be completed in August. Thereafter, three to a maximum of four groups of healthy volunteers will be dosed with three to four different dose levels. Each individual receives one dose a day for two weeks. When the results of a dose group become available, a safety committee will assess whether it is possible to proceed to the next dose level. SynAct Pharma will provide ongoing status reports during the continued implementation of the study, which is expected to be completed around year-end 2018/19. Assuming continued good results in terms of both safety and pharmacokinetics, the project is planned to proceed into a Phase II clinical study in patients with active inflammatory disease (with a focus on rheumatoid and psoriatic arthritis) in the first half of 2019.
What safety data has been generated for AP1189 so far?
At present, more than 50 healthy subjects have been dosed with AP1189 within the framework of the ongoing Phase I study. The study’s safety committee, which has the specific task of reviewing all data before deciding to advance to higher dose levels, has found no safety problems with the candidate drug. In the first part of the single ascending dose study, exposure to the drug at the highest dose level was more than 10 times that expected during therapeutic dosing. In the first group of healthy volunteers who received 14 daily doses of the tablet, the highest measured concentration was more than 3 times that expected for a therapeutic dose.
Will the current suspension be usable in Phase II studies?
A slightly modified preparation of the suspension can potentially be used in Phase II studies. In parallel with the continued Phase I study, SynAct Pharma is initiating the development of an improved oral formulation (tablet). This is to maximise the attractiveness of the project among potential acquirers or licensing partners, and to minimise the overall development time until potential market approval.
When is the Phase II study expected to start
Provided that the outcome of the remaining part of the Phase I study is good, the Phase II study may start as soon as a new oral formulation is available. At present, this is expected to occur in the first half of 2019 and can therefore consist of a tablet preparation or a modified suspension preparation for patient studies.
Why did SynAct Pharma choose to transition from a suspension to a tablet at such an early stage?
A tablet or other solid formulation is the commercially preferred way of administering an oral drug like AP1189 and would be the preferred dosage form of the drug.
Does the return from tablet to suspension change the overall risk profile of the project?
The company does not consider that the overall risk profile of the project has changed due to the unsatisfactory results of the experimental tablet formulation, although a tablet formulation is the commercially preferred dosage form. However, with the suspension, SynAct Pharma has a formulation that provides a very attractive plasma profile and a formulation that ensures that SynAct Pharma can complete the Phase I study. This means that the project has not been delayed due to lack of absorption of the drug, but because of incorrect formulation of the tablet. Getting the right formulation ready for the Phase II study is therefore a matter of using a formulation like the suspension, which ensures fast and reliable absorption.
Does SynAct Pharma have sufficient funds to take AP1189 further through Phase II?
SynAct Pharma has a stable financial situation with sufficient liquid funds to cover the costs of the final part of the Phase I study, the development of a new formulation and the implementation of a Phase II study. However, this may require some internal reprioritisation.
What do the lock-up agreements for the main owners look like?
The company’s principal owners Thomas Jonassen, Jeppe Øvlesen, Torbjørn Bjerke and Henrik Stage (via a company) have pledged not to dispose of more than 10 percent of their shareholding over the next 12 months, starting from March 2018 through the use of lock-up agreements. The Board of Directors and management have invested significant funds in all funding rounds in SynAct Pharma and remain committed to a long-term investment.
For further information about SynAct Pharma AB, please contact:
Jeppe Øvlesen
CEO, SynAct Pharma AB
Telephone: +45 28 44 75 67
E-mail: [email protected]
Thomas Jonassen
CSO, SynAct Pharma AB
Telephone: +45 40 15 66 69
E-mail: [email protected]