focal segmental glomerulosclerosis

They just have nephrotic syndrome.

So it could be primary FSGS, minimal change disease, or membranous nephropathy.

So essentially what do you do is that you investigate on those lines.

Okay? And investigating on those lines means that, you know, you would have to send the PLA2R antibodies, and you would have to flag it up quickly to the renal, uh, people so that, you know, this guy can be biopsied.

So albumin is relatively preserved in patients with, uh, uh, secondary nephrosis, like diabetes.

So they can have seven seven grams of protein urea, but a relatively stable albumin.

Secondary FSGS for that matter, any etiology like long-standing hypertension or any other stuff, uh, it can give you horrible protein urea with relatively preserved albumin.

Same with membranous in the setting of malignancies or infections and all of that.

CSL has entered a global partnership with Allentis Therapeutics worth up to $1.56 billion.

paying $355 million up front to co-develop Lixu-DeBart, a first-in-class CLAUDIN-1 targeting agent, through a Phase III trial in AAVR-PGN and Phase II studies in FSGS and PSC, with CSL taking 55% of profits to Allentis' 45%.

Separately, Jiangsu Nua Pharmaceutical licenses, a clinical-stage sleep disorder asset from Somnivera for $10.5 million up front and up to $507 million in milestones, taking a 15% equity stake while retaining rights in mainland China, Hong Kong, Macau, and Taiwan as Somnivera holds the rest of the world.

Finally, Corksell Chief Medical Officer Bo Liang calls out the most surprising development in obesity medicine over the past decade.

Well, I suspect this is, again, where we will see potentially a difference in disease mechanism, like that second hit question versus maybe this is more of a high risk genotype on a certain genetic background or with certain environmental factors that kind of promote disease.

I suspect that definitely in the cases of like HIV or lupus or membranous nephropathy, where these genotypes seem to be correlated with maybe worse outcomes or higher risk, I suspect there's probably a second hit within that disease process that's stimulating or contributing to the APOL1 kind of genotypic effect, because we certainly see in studies that kind of cytokines and inflammatory markers kind of trigger that kind of toxic gain of function, APOL1 genotype, right? This is the, you enter this kind of toxic feedback loop with APOL1 And so I suspect in kind of those more autoimmune type of presentations and probably also with collapsing FSGS, although again, we maybe understand a little bit less of that presentation, that that upstream inflammatory effect is going to play a role.

And so I think that is those disease phenotypes that are not silent likely may be triggered by a bigger kind of second hit sort of disease physiology versus, you know, maybe hypertensive APOL1 disease, which tends to be more silent, I think is maybe more based on sort of you know, the underlying genetic background for which the APOL1 genotype is layered on top or more of a environmental sort of triggering background that's not necessarily inflammatory.

I think there's definitely a possibility that those more silent diseases and the more kind of in-your-face ones are different in sort of what the underlying cause is.

So do you think this is going to be eventually thought of the way we think of FSGS, where we have like a primary and then secondary categories? Or do you think that it'll be thought of differently?

I suspect that we will start thinking of these diseases as different.

How they will be broken up or labeled, I'm not sure.

I think I wouldn't be surprised if we started classifying them as APOL1-mediated FSGS or APOL1-mediated hypertension or something to that effect, especially as the therapies develop further.

It's estimated about 250,000 people in the US with this variant.

Um, we've previously seen really impressive data in these patients, um, with focal segmental, um, glomerulosclerosis or FSGS patients, um, uh, with these APOA1 alleles.

But there's been a lot of underlying questions about how broadly applicable it'll ...

I- it's, uh, um, across people with the underlying genetics, not just, um, APOL1 and FSGS.

So Meis, uh, which was up a lot on this data this week, they had data earlier this year a- across, um, more diverse patients inclusive of diabetics, uh, non-FSGS patients with their own potentially competitive drug and, and it was kind of mixed.

I think, uh, you know, Meis, Meis went down pretty significantly on their data.

Um, the FSGS patients looked really good in line with, like, what we'd seen from Vertex, but non-FSGS patients, um, the results were a little more confounding, and in diabetics in particular, it really didn't look like it was moving the needle.

Um, so you know, it sort of raised some questions to A, would it be competitive with Vertex's drug, and, and B, if the market would, would wind up including, um, non-FSGS patients, diabetic patients.

So here's what I think about SIDH.

I see SIDH as sort of the FSGS of electrolyte disorders.

Why do I say that? Because, you know, yeah, Josh, you're going to put aside that.

You should like this, right? What is FSGS? It's a pattern of injury.

We have photocyte disorders, hyperfiltration, whatever injury leads to this pattern of injury.

And SIDH is kind of like that.

So in many ways, almost a standalone IgA nephropathy study.

About 200 people with FSGS, and we have data on primary and secondary FSGS as reported by their clinicians.

About 90 patients with membranous as well as a range of other less common glomerular diseases.

And these patients, as you would expect, they were typically younger, more likely to be female, had a higher GFR and higher levels of proteinuria, and higher SGLT2 inhibitor use at baseline.

And what we did was we spent a lot of time across the study sites and countries collecting information on these individuals.

When was their biopsy? What did they, in some cases, we tried to get, you know, MES-C scores.

And then, as I said, information about primary and secondary FSGS.

So we tried to collect as much information as possible so that the results would ultimately be useful to patients and clinicians.