I know it gets tiring to read the endless complaints about the passing of time with no news. There are some who say they've done their DD and have come to the conclusion that Bioasis has failed. Obviously these people don't know what they're talking about. Those who complain the loudest appear to have the least knowledge about the scope of preclinical work and how long it takes to get drugs through preclinical programs to the point of IND submissions to the FDA. Let's take a brief look at preclinical work.
Bioasis appears to have several programs on the books that could be at various preclinical stages. They involve Chiesi (1 of 4 LSDs), Aposense, Oxyrane, and Daiichi Sankyo. There are probably more, especially with Aposense and Daiichi Sankyo. Also, Chiesi, with Protalix, may be involved in more. We also have the major Bioasis pipeline programs - xB3-001, xB3-004, xB3-007 and xB3-progranulin. All of these have had at least some preclinical work completed.
The partner programs, as I predicted years ago, are pretty much all secret. However, there is one thing we can assume about all xB3 drug programs. All of the Bioasis pipeline PAYLOADS and the PAYLOADS of the company's partners are all mature payloads, meaning that they are all well-researched and developed drugs that should be worth transporting into the CNS. This means that preclinical discovery work for all xB3 drugs should be mostly complete. For instance, xB3-001's payload, trastuzumab, is known to work. As a result, no basic discovery work is needed for xB3-001.
I've put together a list of the preclinical steps that are likely remaining for all the drugs. Each of the steps requires considerable time to execute. They all require planning, allocation or contracting of people and other resources, execution and assessments of results. Very few of these steps can be started until the previous steps have been completed.
We might expect the xB3-Drugs to be going through the following phases:
- Design, with Bioasis input, the structure of the fusion protein or conjugate. (Takes time)
- Manufacturing of the new drug in quantities sufficient for preclinical testing.
- Early In vitro testing for:Pharmacodynamics (what the drug does to the body), Pharmacokinetics (what the body does to the drug), ADME (absorption, distribution, metabolism, and excretion), and toxicity.
- Animal testing for: Pharmacodynamics (what the drug does to the body), Pharmacokinetics (what the body does to the drug), ADME (absorption, distribution, metabolism, and excretion), toxicity, and dosing amounts and strategies.
- Development of human clinical trial strategies.
- Design of Phase 1 clinical trial.
- Manufacturing processes must be developed that can produce commercial quantities of the drug with the drugs having reproducible structures. This requires substantial manufacturing facilities, cell lines that consistently produce the required fusion protein structures, post expression processing, and quality assurance systems to prove to health authorities that the drugs remain within GMP (good manufacturing practice) standards.
- Final preparation of IND submission to FDA.
As you can see, there's a lot of work to do. It's known that considerable preclinical work has been done with xB3-001 and xB3-004. Bioasis has made a pre-IND submission to the FDA for xB3-001. We have seen qualitative (no data) results for xB3-004. xB3-progranulin is close behind. I would expect that Chiesi is somewhat advanced on at least one LSD. Companies like Chiesi don't pay a bunch of money to do nothing. Daiichi Sankyo appears to have time limits on its exploratory work, but as with all preclinical work, a serious problem with a drug can cause a preclinical program to be abandoned.
Work that is being undertaken with some partners is likely being done so under
Material Transfer Agreements. These agreements usually have limited scope and time limits, requiring more complex agreements for more serious work to be undertaken.
Preclinical programs are obviously big projects. Bioasis is deep into a number of preclinical programs with its own pipeline and with partners' programs. All of these, except for xB3-001 and, maybe, xB3-007 (MPS II), have been started on DrDR's watch. Before any of them could be started they needed to be created, scoped out, patents applied for, and a host of other time-consuming activities completed. And yet, here we are, with several preclinical programs underway. I fully expect these programs, both in-house and with partners, to generate results and deals in the weeks and months ahead. It's also likely true that no amount of money and effort could have produced more results than we've seen so far.
The message, therefore, is that complaints about timelines are likely unfounded. If we don't see some interesting stuff in the short to mid term then go ahead, get cranky, but I don't think there's a legitimate timeline complaint to be made just yet.
Ignore the complainers. If they had done any real DD they wouldn't have anything to complain about.
AIMNVHO (All in my never very humble opinion)
jd