Hey Ganesha. I have some thoughts on the 700mg dat

Hey Ganesha. I have some thoughts on the 700mg data.

The reason any drug that you or I might take is at a specified dose is because through trials the company marketing it figured out what dose best maximized efficacy while minimizing side effects. Because just about every drug has some level of side effects, and those side effects tend to have a linear relationship to dosing, there's always an effort to give just enough to work properly.

Leronlimab is a little different (no severe adverse events!) but the initial process is still the same. Through trial and error, calculations based on lab/mouse studies, and a whole lot of discussion in a stinky break room littered with used Cytodyn coffee mugs, they determined that 350mg was the right dose. As it turns out, Leronlimab is quite safe to take. Upping the dose to 700mg or giving it through an IV doesn't increase the side effect profile like other drugs might. It gets you more drug and/or faster drug into your system though.

We've seen through trials, heard through conference calls, and experienced through fever dreams how 700mg is probably more optimal in terms of efficacy. Ohm or others can break down the receptor occupancy for you, but basically we know now that in comparison to 350mg, the 700mg dose is probably more effective and definitely no less safe. We see evidence of that in HIV and Cancer trials. Why not in Nash?

But that wasn't even your concern necessarily, that it's better. You're worried it's worse than 350mg and I understand the concern based on how trial results have been disseminated in the past, and how we keep getting hosed on some minor or major details. In this case, however, I don't share your worry.

With everything we know about 350mg versus 700mg we should at least expect the higher dose to perform as well, if not better. There's nothing in the science or our trials to suggest that going up in dose is worse. It's always been better as far as I can tell. Now that's not saying that from one condition to the next you may find that 350mg maxes out a result just fine and doubling the dose does nothing more for the patient. That's certainly possible, as different conditions require different intensities and durations of treatment to resolve. Like how some infections require a longer or stronger dose of antibiotics than others.

With our Nash trial at 700mg there should be no concern of negative results, since half the dose already showed that it works. We should see either the same results, or better results. I'm anticipating better results, though it may only be slightly better. Hard to know definitively. What I have no fear of is underperforming compared to 350mg. There's just nothing beyond fear of failure that justifies that possibility.

Caveat: Sometimes a trial design flaw or randomization issue will derail a study (CD10 and CD12) and that kind of thing can't be discounted. But that wouldn't be a knock on LL's potential, just a knock to our collective junk as investors that we'd need yet another stretch of time to recover from. Plus the 350mg arm succeeded in this trial design already, so there's some evidence that we'll be ok. After all, why would patients stop responding to the drug just because we injected twice as much?