“Here, we provide visibility into the steady cadence of milestones expected over the next 12 months, including 5 regulatory decisions, 8 key readouts and 19 pivotal study starts.”

In context

“Chris Boshoff (Chief Scientific Officer): Thanks, Cecile. I will now provide additional color on the past quarter. Starting with the recent Phase III readout for Litfulo in nonsegmental vitiligo, a condition affecting more than 1 million adults in the U.S. alone. In the TRANQUILLO program, both the 50- and 100-milligram doses of Litfulo delivered significant clinically meaningful improvements over placebo on co-primary endpoints for the facial and Total Body Vitiligo Area Scoring Index, or VASI. Specifically, the program measured the percentage of patients that achieved a certain percent improvement from baseline, 75% for facial VASI and 50% for total VASI at week 52. On the right, data for Litfulo, an internally discovered molecule with unique mechanism of action targeting TEC family kinases and JAK3, alongside results from recent pivotal trials of oral JAK1 selective inhibitors. These data show placebo-adjusted percentages of participants achieving facial VASI75. At the 100-milligram dose, Litfulo induced a placebo-adjusted response rate of 19.5% at week 52. While cross-trial comparisons cannot support definitive conclusions, we're encouraged when viewing these facial VASI results alongside external comparator data. Management of vitiligo requires continued and durable treatment, which is why we are particularly encouraged by emerging data from our extension study demonstrating a sustained treatment effect with continued dosing at 100 milligrams after two years. Moving to oncology. I'll start with Padcev, the transformative bladder cancer medicine from our Seagen transaction. Last month, the FDA expanded the approved indication of Padcev plus pembrolizumab to muscle invasive bladder cancer regardless of cisplatin eligibility. The expansion was based on Phase III results showing a 35% reduction in the risk of death versus standard of care. Together with prior data showing unprecedented survival benefits in the cisplatin-ineligible muscle invasive and locally advanced or metastatic settings, these results establish Padcev as a potential practice-changing medicine for more than 42,000 patients in the U.S. alone. This quarter, we also initiated a Phase III trial in the bladder-sparing muscle invasive bladder cancer setting, aiming to extend Padcev transformative benefits even further and to offer an option for patients seeking to avoid cystectomy. Combined with our leading capabilities in small molecules and protein engineering, we are now advancing the next wave of potential ADC breakthroughs in the clinic, leveraging innovative linkers, payloads and targets. Two I will highlight. GPS, which includes an auristatin S payload designed for improved tolerability and 3028 from Innovent, a bispecific dual payload ADC integrating multiple clinically validated approaches. With these and other programs, we aim to cement Pfizer as a leading developer of ADCs, maximizing the value from recent transactions. In June, we announced the primary overall survival endpoint was not met in the intention to treat population non-small cell, non-squamous non-small cell lung cancer. Though a disappointing outcome, we were encouraged that the subgroup of patients who received only one prior line of therapy showed a median survival benefit of 2.5 months, 13.6 with SV versus 11.1 months with docetaxel. This suggests a survival benefit that is meaningful for patients. For context, standard of care ramucirumab plus docetaxel was approved based on a survival benefit of 1.4 months in its pivotal second-line trial, though no definitive conclusions can be drawn across studies. Together with updated Phase I data we are sharing today, these results reinforce that SV has the potential to deliver meaningful activity in earlier lines of lung cancer. On the right are updated Phase I data of SV plus pembrolizumab in first-line non-small cell lung cancer with high PD-L1 expression, the same regimen and indication as our ongoing Phase III trial. These data show robust activity with an unconfirmed objective response rate of about 82%, including a complete response. This compares favorably to historical anti-PD-1 monotherapy. These data align with the ability of vedotin ADCs to induce immunogenic cell death and thereby potentially synergize with anti-PD-1 agents such as pembrolizumab. We've seen meaningful activity when combining vedotin with immune checkpoint blockers in our Padcev, Tivdak and Adcetris programs, and we aim to extend this finding in SV's ongoing Phase III trial. Moving to 4404, our PD-1 VEGF bispecific antibody that has the potential to be a next-generation backbone therapy. Of note, the ongoing Phase I dose escalation study of 4404 in combination with SV is showing early and encouraging response rates. Since in-licensing from 3SBio about a year ago, we started 9 trials, including 2 Phase III studies. We have expanded the program's global reach with approximately 230 patients dosed outside of China to date and are encouraged that the safety profile has remained consistent. Our goal is to develop 4404 as a potential best-in-class foundational therapy across multiple tumor types. Our ambitions with 4404 supported by its differentiated profile recently presented at AACR, including in vitro data showing soluble VEGF-A affinity that is 30 to 60-fold higher than the PD-1 VEGF bispecific ivonescimab and the VEGF monoclonal anti-bevacizumab. Our Phase II data remain encouraging at a selected pivotal dose in first-line PD-L1 positive non-small cell lung cancer, 4404 monotherapy generated a confirmed response rate of about 68% and median progression-free survival of about 12.4 months. As you can see on the right, these data compare favorably with ivonescimab's Phase III results in this population, though cross-trial comparisons preclude definitive conclusions. Moving next to mevrometostat, our potential first-in-class internally discovered EZH2 inhibitor. EZH2 is the core catalytic subunit of the polycomb repressor complex 2, PRC2. Mevrometostat is currently in Phase III development and the next potential breakthrough in our prostate franchise, including XTANDI and TALZENNA. Mevrometostat targets the underlying epigenetic mechanisms that drive resistance to andro receptor pathway inhibitors such as XTANDI. We are encouraged by the randomized Phase I data in post-abiraterone hormone-resistant prostate cancer, showing radiographic progression-free survival more than doubling with mevrometostat plus XTANDI versus XTANDI alone. This translated to a 49% reduction in risk of disease progression or death. We are taking a comprehensive approach with Mevrometostat's development with 3 pivotal studies underway, including MEVPRO-1, evaluating Mevrometostat plus XTANDI versus either XTANDI or docetaxel in post-abiraterone metastatic hormone-resistant prostate cancer. Each of these studies is event-driven with the first readout expected for MEVPRO-1 in the fourth quarter based on the current event rate. In MEVPRO-1, our goal is to delay resistance to XTANDI, which has historically delivered radiographic progression-free survival of about 5 to 8 months in similar settings. Obesity is a core focus area for our R&D organization. In June, we presented Phase IIb data supporting berobenatide's potential as a first-in-class monthly GLP-1 receptor agonist peptide and foundational metabolic medicine. Shown here are Phase IIb ADA data on monthly berobenatide at 4.8 milligrams, which is our medium Phase III dose. At this dose, we achieved placebo-corrected weight loss of up to 12.3% in our VESPER-3 trial. Though cross-trial comparisons cannot support definitive conclusions, it is encouraging that berobenatide achieved week 28 efficacy that was similar to tirzepatide's medium dose of 10 milligrams in the SURMOUNT-1 study and potentially better than semaglutide's medium approved dose of 2.4 milligrams in STEP 1. We also presented the first results at our high Phase III dose, 2.4 milligram weekly or 9.6 milligrams monthly from Phase IIb VESPER-1 extension participants who escalated from placebo to 2.4 milligram weekly berobenatide. Participants achieved approximately 16% mean weight loss over 32 weeks of treatment. Importantly, there were no treatment discontinuations due to treatment-emergent adverse events in any of the arms evaluating maintenance doses moving to Phase III. On the right is a model-based meta-analysis of data from over 32,000 participants to project 72-week weight loss for berobenatide's high monthly Phase III dose relative to the highest approved doses of tirzepatide and semaglutide. As with our clinical data from VESPER-3 monthly study, the analysis suggests berobenatide can deliver weight loss comparable to tirzepatide and potentially better than semaglutide. We see high concordance between the high-dose VESPER-1 extension study and the model's predictions, further increasing our confidence that berobenatide can potentially deliver robust efficacy and favorable GI tolerability with the convenience of a monthly therapy. Since closing the Metsera transaction about 8 months ago, we've advanced berobenatide towards the first of a series of potential approvals beginning in 2028. Today, we have 3 ongoing Phase III trials. The now fully enrolled VESPER-4 and 5 studies of weekly berobenatide and the VESPER-6 study evaluating monthly dosing. We plan to advance 10 Phase III studies in 2026, including one evaluating participants switching from approved weekly therapies to monthly berobenatide. Our obesity portfolio includes injectables with the potential for monthly or longer dosing, once-daily orals and novel combinations. The most advanced combination is berobenatide plus the ultra-long-acting amylin analog 3945, which we are developing as potential first-in-category monthly medicine. We expect to report data from Phase I/IIa studies of 3945 monotherapy and berobenatide combination this year. As is typical for small early-stage studies, these were designed to inform starting doses and potential escalation regimens for further evaluation in Phase IIb. Our Phase IIb SOLIS-1 study has already enrolled more than half of approximately 900 planned participants. We expect data from SOLIS-1 in 2027, providing us with the first robust efficacy data from our amylin monotherapy and combination programs. Looking ahead, our efforts in R&D will continue to be defined by focused execution. Here, we provide visibility into the steady cadence of milestones expected over the next 12 months, including 5 regulatory decisions, 8 key readouts and 19 pivotal study starts. With that, I'll hand it over to Albert.”