MSL: Good morning, Dr. Martinez. Thank you for meeting with me today to discuss our IL-17A/F inhibitor for psoriatic arthritis.

Dr. Martinez: I've been interested in this mechanism, especially since it targets both IL-17A and F. How does that translate clinically compared to the IL-17A inhibitors we already have?

MSL: That's an excellent question. In our head-to-head trial against adalimumab, we saw superior efficacy on skin endpoints, with PASI 90 rates of 65% versus 42%. For joint endpoints, we demonstrated non-inferiority with ACR20 responses of 58% versus 57%. The IL-17F component appears to provide additional benefit for skin manifestations while maintaining joint efficacy.

Dr. Martinez: Interesting. I often see patients with both peripheral and axial disease. Do you have data specifically in patients with axial involvement?

MSL: We have a subgroup analysis from our phase 3 program that included patients with physician-diagnosed axial disease. In this population, we saw improvements in ASDAS scores similar to what's been observed with IL-17A inhibitors in ankylosing spondylitis. We're currently running a dedicated phase 3b study in psoriatic arthritis patients with axial disease with MRI endpoints.

Dr. Martinez: That's helpful. What about enthesitis? That's often a challenging aspect to treat.

MSL: We observed complete resolution of enthesitis in 62% of patients by week 24, which was significantly better than the 41% seen with adalimumab in our head-to-head study. Our preclinical models suggest that the dual inhibition of IL-17A and F may be particularly effective for entheseal inflammation.

Dr. Martinez: Safety profile is always a concern. What have you observed with Candida infections and IBD, which have been signals with IL-17 inhibitors?

MSL: Candida infections were observed in 4.2% of patients, primarily mild to moderate oral candidiasis responsive to standard therapy. For IBD, we didn't observe any cases of new-onset Crohn's disease in our clinical program. There were two cases of ulcerative colitis flares in patients with pre-existing disease, which is consistent with the background rate.

Dr. Martinez: Good to know. Many of my patients have comorbidities like metabolic syndrome. Any data on impacts on lipids or glucose metabolism?

MSL: We haven't observed any clinically meaningful changes in lipid parameters or glucose metabolism. In fact, we're conducting a metabolic substudy looking at changes in insulin sensitivity and body composition, with results expected next year.

Dr. Martinez: I'm particularly interested in long-term radiographic outcomes. Do you have any data on structural progression?

MSL: Our 2-year radiographic data showed 90% of patients had no radiographic progression, defined as change in mTSS ≤0.5. This was maintained through year 3 in our open-label extension. We're continuing to follow patients for up to 5 years to assess long-term structural outcomes.

Dr. Martinez: What about immunogenicity? That's been an issue with some biologics.

MSL: The immunogenicity rate was 5.3% through week 52, with no apparent impact on efficacy or safety in those who developed anti-drug antibodies. This low rate is likely due to the molecule's unique structure, which was engineered to reduce immunogenic epitopes.

Dr. Martinez: Very helpful. I've noticed some variability in response to IL-17 inhibitors in my practice. Any insights on predictive biomarkers?

MSL: We're exploring several potential biomarkers. Preliminary data suggest that baseline expression of Th17 pathway genes in peripheral blood correlates with skin response, while synovial IL-17F expression may predict joint response. We're collaborating with academic centers on a precision medicine approach using multi-omics.

Dr. Martinez: That's the direction we need to move in. One last question - what about vaccination? Many of my patients are concerned about this, especially with COVID.

MSL: Our data show that humoral responses to both pneumococcal and influenza vaccines were preserved in patients on treatment. For COVID vaccines, we have preliminary data suggesting similar antibody titers compared to healthy controls, though with a slight decrease in T-cell responses. We recommend following standard vaccination guidelines with no contraindication to non-live vaccines.

Dr. Martinez: Thank you for the scientific exchange. This helps me better understand where this therapy might fit for my patients.

MSL: I appreciate your thoughtful questions, Dr. Martinez. I'll send you the publication on the axial subgroup analysis we discussed.