Something else to consider with respect to timing….. At last...

Something else to consider with respect to timing…..

At last year’s AGM it was explained that the Lanstead funding arrangement would enable the company to commit to initiating key manufacturing and non-clinical activities that had to be completed before commencement of the Ph 3 trial.  The cash flow for these activities was to occur across both H2 2017 and H1 2018. The key activities were:

• Conclude the optimization of the drug substance manufacturing process for commercial supply
• Conclude the stability testing and analytical validation of the new to-be-marketed liquid drug formulation
• Conduct a 6 months’ dosing toxicity study in rodents, which is required for a Phase 3 trial and subsequently to support a New Drug Application to the FDA

The first two activities were apparently ongoing; it was said that they still had to be concluded. The reference to the 6 month toxicity study in rats suggested it was still to be conducted (commenced?)
In the Investor Presentation released on 6 October, just before the meeting with the FDA, the wording in reference to the toxicity study hadn’t changed. Following the meeting with the FDA, the 13 October announcement stated that, as the FDA had now provided “necessary confirmation on the key issues relating to our proposed Phase 3 trial in Rett syndrome”, the company was now able to progress “the final stages of development with full confidence”. Was the toxicology study perhaps part of the final stages of development?

My understanding (from what I have read) is that the dosage used in the chronic toxicity study is calculated with reference to the dosage that is proposed in humans (in the Phase 3 trial and thereafter, if approved). If that’s correct, wouldn’t it be necessary to wait for the FDA’s confirmation of NEU’s Ph 3 plan (including dosage) before commencing the toxicity trials? Also, if you were a pharma proposing to pay big dollars to take on trofinetide, wouldn’t you prefer to first see the toxicity study box ticked as successfully completed?

If the 6 month rodent toxicity study commenced shortly after the FDA meeting, it would not conclude before late-April….