I have decided that I'll be getting into this one in the coming months.
From what I can see, there is a lot to like.
While flaviviruses afflict millions of people each year, there is currently unmet clinical need for drug therapies. Also, ISLA-101 is eligible for Neglected Tropical Disease designation for the treatment of dengue fever, which means that it can earn a priority review voucher (PRV) from the FDA if first approved for dengue or Zika virus. Priority review vouchers have historically sold for around USD $100 million.
Fenretinide (or 4-HPR) is a synthetic retinoid that has been investigated in the clinic in adults and children as a potential treatment or preventative for various cancers, psoriasis, obesity-associated insulin resistance, and macular degeneration. I've shared the table below before, but it is a summary of clinical research investigating 4-HPR's effectiveness in humans.
More recent dataRecent discoveries have identified that 4-HPR has unique antiviral activity, particularly in dengue and Zika viruses. I have attached a summary of preclinical investigations into 4-HPR. The research is a little different to what I am used to, so apologies if this is a little messy. If you are unfamiliar with some of the terminology, google is your friend. Put simply, a relatively low dose (low uM range) of 4-HPR is required to inhibit the dengue and Zika viruses, which has been confirmed by individual research groups and duplicate publications. The doses used in animals range from 20 mg/kg to 180 mg/kg, and it appears that frequent dosing during the day confers the best effect. Also, the dose used in these studies are within the historic doses used in people, ranging from ~60 mg/m2 to 540 mg/m2.
Some more specific things that caught my eye were:
1. The efficacy of 4-HPR on inhibiting dengue virus while maintaining cell viability.
2. Twice daily 4-HPR administration led to ~70% survival in mice.
3. The consistency of effect across tissue types.
4. The unique mechanism of action not being influenced by GTP introduction and common antiviral resistance, as well as showing some function in other virus types like Kunjin, Modoc, HCV, vesicular stomatitis virus (VSV), and poliovirus 1 (PV1).
Current company I think that the near-term news flow is great and the company has hit the ground running with an established drug. Since preclinical data supports a dose that has already been trialed in humans, there is substantially reduced risk associated with safety. The phase II trial design should provide a return on data very quickly (unlike cancer trials!). They have structured the trial design similar to how preclinical studies have determined efficacy in vivo - minus harvesting organs, of course! (example below ILA phase II trial protocol). I'm assuming that they will be investigating whether treatment in humans confers the same response in animals, whereby 4-HPR inhibits dengue RNA replication as well as the production of dengue core and NS3 proteins.
CompetitorsI am struggling to find any competitors, so I can compare market caps and determine potential fold increase from here. If people have this data and are willing to share, it would be great if you could do that here. Something I can comment on is a trial compared 4-HPR to celgosivir, where it outperformed it. At the time, celgosivir was going through P1b trials (dose escalation), but it seems like there is little new data out there available now. Since it's not recognised as a treatment for dengue, I'm assuming it didn't go well.
All in all, this looks like a great opportunity.
