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This is an ACR twenty twenty five podcast coming to you from Chicago. Hope you enjoy it.

Hi. I'm Jack Cush here on the Convention floor at ACR twenty twenty five. I'm joined by Doctor. Angelica Jaris, who's from Novartis. Angelica, introduce yourself to the audience.

Hi, my name is Angelica Jaris. I am the Development Head for Immunology at Novartis.

Yeah, so I invited Angelica here to talk about some exciting new things that are happening that's gonna be presented at the last day of the meeting here on their B cell targeted drug. Say it again, say it for me. Yanalumab. Yanalumab. It's I A N, Yanalumab.

A novel compound, it's been out there in clinical trials. How did this drug get going at Novartis? What's its history?

Yes, we have developed that across a variety of diseases. Initially for ten years, we've had a focus in Sjogren's disease and B cell targeted seemed to be a good area for Sjogren's disease. So we developed a molecule, in licensed the molecule, that had a dual mechanism of action. On the one hand side, it is an afrocucilated molecule that depletes B cells. And we also have a poster here that shows you that the B cell depletion is very deep in the tissue as well as in the periphery.

And then it inhibits the BAF signaling by blocking the BAF interaction with the BAF receptor on the B cells. So the B cell stimulation and activation of those remaining B cells in the tissue is also inhibited. So it has a really important dual mechanism of action. And that led to interesting phase 2B data where we have seen a good effect, a significant effect on the SI in our phase two studies. So disease activity is reduced with cianalumab in the phase two studies which made us then go forward and conduct two large global phase three studies.

And those are the Neptunia studies that are being presented here. Why two? What's different about Neptunias one and Neptunias two?

They are replicate studies because in order to seek regulatory approval, we wanted to have two adequate and well controlled studies. They are both global studies. One of them is only looking at enalumab monthly dosing versus placebo on background standard of care, whereas the other study is looking at two different dosing regimens, Yanalumab monthly dosing, as well as Yanalumab every three months dosing versus placebo. But they are replicate studies so that we can file with the evidence that's necessary for regulatory approval, which is too adequate and well controlled global So this is

a very novel It's got sort of dual mechanism. It's a good B cell depleter. Other than those factors, this is novel in that you have positive successful results in a phase three trial in Sjogren's.

Yes.

Is it just because of that, why do you think you're so successful when others have failed?

I think it is the dual mechanism of action most likely that we are depleting B cells in the tissue. I think in other diseases that has also been demonstrated that it's important to really block the B cells and deplete the B cells in the tissue of interest as well as then with the dual mechanism blocking the survival factor for B cells. So it has a very profound effect on B cells. And I think that is one of the reasons why we have two successful studies now. We were able to reduce the SDI score which measures disease activity in those patients with Sjogren's disease who had systemic manifestations of Sjogren's.

So I do think these are landmark studies because after two decades of really trying to find new treatments for Sjogren's, including us at Novartis.

Right.

Now for the first time, we have two successful studies that met the primary endpoint.

In addition to the phase two that looked really good?

Yes, in addition

to the In addition phase to, enalap working also well in lupus and other areas of investigation right now, is that right?

Yes, we have a phase two study also in lupus where we think that the data are very promising and we are conducting currently a phase three study, two phase three studies in lupus, a phase C study in lupus nephritis, as well as a study in systemic sclerosis. So we really think that this molecule has prospect across B cell mediated diseases.

So Novartis Immunology is very, very busy. You also getting into CAR T?

We are. And I wanna say we are excited about the prospect of CAR T in severe refractory, in patients with severe refractory autoimmune diseases. We currently have six studies ongoing and we really want to partner with rheumatologists and with patients with rheumatic diseases to advance this therapy forward. And we are looking for investigators who are interested to join us in that partnership so that we can assess the risk benefit of CAR T cell therapies for patients with rheumatic diseases.

I encourage the audience to look into the Neptunis results, both primary endpoints, secondary endpoints were wins and look very good. Congratulations to Novartis for this.

Thank you so much.

Take care.

Hi. My name is Derek Mueller, PA from Saint Clair Shores, Michigan, and I'm reporting from ACR Convergence twenty twenty five. I attended a very interesting session on underappreciated features of pulmonary sarcoidosis. Doctor Michelle Sharp from Johns Hopkins University, she described her cohort of six hundred and two sarcoidosis patients, of which fifty six percent of those had abnormal PFTs. As expected, a large amount of those patients based on PFT pattern had that of a restrictive pattern, likely due to interstitial lung disease.

So no surprise there. Twenty two percent of her cohort had an obstructive pattern on PFTs, fifteen percent had a mixed pattern, but what I found really interesting was a sixteen percent had a PFT pattern that was that of isolated DLCO only, something that we would see as a association with pulmonary hypertension. So I think that sarcoidosis associated pulmonary hypertension is something that we don't tend to think about. And then actually, after her presentation, doctor Robert Bowman, he described three different features that may predict mortality in pulmonary sarcoidosis. One of those being extensive fibrosis, and then two features include dilated pulmonary artery diameter on HRCT, as well as diagnosed pulmonary hypertension by right heart calf.

And actually that, presence of pulmonary hypertension in sarcoidosis patients, was a increased hazard ratio of mortality, eight point nine six. So pretty striking seeing that association with pulmonary hypertension, sarcoidosis, and mortality. So I think my take home points from this session were, think about pulmonary hypertension in sarcoidosis patients just because they have, unremarkable PFTs, no restrictive pattern obstructive, look at that DLCO and that might predict their mortality. And we should have a low threshold to consider doing additional testing such as echo and referrals of right heart cath for sarcoidosis patients, even in the absence of frank interstitial lung disease.