RE:RE:ShtuffGood questions, Fred. First off, Bioasis has not yet presented a structure to the FDA for IND approval. So it's not like we're presenting a new structure to them; we've presented no structure at all, yet. Secondly, although the new structure was mentioned in the roadshows, it was also stated in the roadshows and is indicated in the current corporate presentation that the pre-IND meeting with the FDA remains scheduled for June. So the new structure hasn't affected that, indicating that our current data will be presented in that meeting.
Taking a look at xB3-001, it consists of the xB3 peptide linked to a trastuzumab structure in the form of xB3<>linker<>trastuzumab. If there was a problem with the xB3 peptide structure then we'd need to get the correction patented, which is not what happened. It was the xB3-001 patent that was replaced. So the xB3 peptide structure stands as patented. Trastuzumab has known and accepted structures, has had for over 20 years. It seems probable that the functional parts of xB3-001 remain unchanged. I don't know what version of trastuzumab we're using, the original or a biosimilar. The existence of biosimilars make it evident that different trastuzumab-like structures exist, suggesting that tweaking of trastuzumab structures is possible and does happen, and that we could also do it. I have reasons to think that was not the case here.
That leaves the linker as the likely issue. Bioasis has detailed several linkers in it patents, linkers for different uses. For instance, we have long linkers for deeper chemical connections within protein folds, shorter linkers for more readily available chemical connections. To my knowledge, the linker does not directly contribute to the mechanism of action (MOA) of xB3-001. However, it's always been my understanding that the choice of linker that Bioasis would make is dependent on the payload. The long linker/short linker option is evidence of that probability. We used a specific linker for xB3-001. If the linker was the problem with WuXi's work, then I would think the problem had to do with stability of the link that may show up only in manufacturing and not necessarily in pre-clinical or clinical applications.
I would think that if Bioasis needs to do any further studies on the new structure then that would be communicated to the company after the pre-IND meeting. It seems clear enough that the Bioasis brain-trust (our scientists, BoD, and SAB) believes that proceding with the pre-IND meeting is appropriate and that the structural changes will not impact, or appreciably impact, the results of that.
With respect to the corporate presentation's use of "xB3-001" to describe mouse studies, it should be noted that the company has animal data for both BT2111 (Mtf-TZM) and for xB3-001 (previously called MTfp-TZM). The latter data were
described in a press release back in 2015. I think it's fair to discuss all those data under the xB3-001 program umbrella.
I suspect I'll be corrected if I'm off base on any of this, Fred, but that's my take on your questions.
jdstox