Hello everyone. Greetings of the day. My name is Karthik Akinnapelli and I'm hoping you're all doing well. Today, I'm excited to share the results of a trial conducted to evaluate a new oral antibiotic in comparison to Emprixiprofloxacin. So why late? Let's dive into the study and look at its key findings. So before we jump into the trial information, let me give you a little bit background of this trial. So why new antibiotic? There is a growing concern about increasing fluoroquinolone resistance in real world settings, which significantly limits treatment options for uncomplicated urinary tract infections in outpatient setting, which leads to hospitalization. Now why sulopenum? Sulopenum is the first oral theopenum antibiotic specifically developed to combat multi drug resistant gram negative uropathogens. Neuropathogens are nothing but pathogens responsible for urinary tract infections. Now about this study. This is a phase 3 double blind study evaluating the efficacy and safety of a five day course of sulopenum compared to the standard three day regimen of ciprofloxacin in adult women with UUTIs. Coming to the end point, the primary end point is a robust composite measure. assessing both clinical symptom resolution and microbiological eradication at the test of cure visit which is day 12 in the study. Now let's look at enrollment overview. A total of 1672 women were enrolled in the trial of which 1660 participants were qualified for the safety population, meaning they received at least one dose of study drug. Whereas 1072 participants qualified into microbiological intent to treat population. This is where the primary endpoint is evaluated. The criteria to qualify into this population is that the baseline pathogen should have at least 10 to the 5 CFU per ml. CFU is nothing but colony forming units. Now, key findings. Essertia coli was the predominant pathogen accounting for approximately 85 percent of all infections in this study. Of these, 27 percent demonstrated non susceptibility to ciprofloxacin. That is pretty high rate. Now second most common pathogen identified was Klebsiella pneumonia. Now, looking at resistance insights, around 13. 5 percent of the total isolates were extended spectrum beta lactamase producing, ESBL producing organisms, indicating multi drug resistance. Now, let's look at efficacy results. in non susceptible pathogens. Sulopenum demonstrated clear superiority over ciprofloxacin in treating non susceptible pathogens with a significant treatment difference in efficacy of 26. 6 percent and a highly significant p value. Now, in susceptible pathogens, sulopenum did not achieve non inferiority. The response rate for sulopenum was 66. 8 percent in solo. compared to 78. 6 percent in Cipro. Now in overall study population combining both non susceptible and susceptible populations, solopenem achieved non inferiority with the response rate of 65. 6 in solo compared to 67. 9 in ciprofloxacin. So let's look at clinical response. The study evaluated clinical response at various time points with the following key findings. At initial evaluation at day 5 of the study, solopenem and ceprofloxacin demonstrated comparable response rates, 68. 7 percent solo versus 67. 3 percent in cipro. At day 12, which is at, Primary endpoint, solopenem showed similar overall effectiveness in clinical response compared to ciprofloxacin 81. 1 percent in Sulo versus 84. 1 percent in Cipro Whereas in the resistant population, solopenem clearly exhibited superior efficacy 83 percent in Sulo versus 62. 6 percent in Cipro Now they also evaluated a follow-up period, which is day 28. Both treatment groups maintained a sustained clinical response confirming the durability of the treatments. Now with good clinical response, why did Opinum did not achieve non-inferiority in non susceptible pathogens? This is because of a SP impact. Like I said, while clinical response rates are very comparable between two treatment groups, the difference lay in microbiological outcomes, specifically the occurrence of ASB, asymptomatic bacteria, which is nothing but patients are clinically clear, but has a positive culture. Now, at day 12, ASB was more prevalent in sulopinem group compared to ciprofloxacin. 15. 2 percent in Sulo versus 7. 8 percent in Cipro. Despite the higher ASB rates, patients in both groups demonstrated equivalent clinical outcomes during follow up period at day 28, as we saw in the previous slide. This is confirming the durability of the treatment. So what's the conclusion? The higher ASB rates with Sulopenum likely reflect the restoration of normal urogenital bacterial flora. rather than persistent infection highlighting a potential microbiological advantage. Now, let's look at resistance emergence. So, some of the key observations include resistance development. Following treatment with ciprofloxacin, 41. 7 percent of initially susceptible pathogens developed resistance. very high percent indicating significant selective pressure. Now genetic changes in pathogens post treatment some pathogens acquired extended spectrum beta lactamase ESBL genes compromising multiple antibiotic classes and further limiting treatment options. Now, looking at sulopenum MIC stability, in contrast, MIC distribution for sulopenum remains stable, demonstrating a low risk of resistance development. So what's the conclusion? The contrasting effects on bacterial resistance patterns underscored the critical importance of antibiotic stewardship and informed drug selection in managing UTIs. These findings highlight silopenum's potential as a valuable option in combating antibiotic resistance. Now, let's look at safety profile. So, both treatment groups showed almost similar safety results. Silopenum showed 25 percent of adverse event rate compared to ciprofloxacin at 14%. And the most common adverse event include headache. which is 4. 2 percent in Sulo versus 3. 1 percent in Cipro. And the next most common adverse event found is nausea. 3. 8 percent in Sulo versus 2. 2 percent in Cipro. Diarrhoea, which is GI related, was significantly more common with Sulopenum at 12. 4 percent versus 2. 5 with a mean duration of three days, but 95 percent of cases resolved spontaneously while 5 percent required anti diarrheal medication. Other GI effects include nausea and abdominal pain, pretty much very common with all antibiotic classes. Serious adverse event rates are also similar, 0. 7 percent in versus 0. 2 percent in Cipro and of the six serious adverse events on solopenem, only two were considered drug related. And in the course of the study, no deaths occurred and all the SOEs are resolved by the end of the study. Now, implications of empirical treatment. Similar overall efficacy. So, solopenum showed non inferiority to ciprofloxacin in general population as we seen in the previous slides. Resistant advantage. Solopenum showed superiority to ciprofloxacin in non susceptible population. Reduce risk resistance. As discussed in the previous slide, solopenum demonstrated low risk of resistance development and giving a treatment option for multidrug resistant UTIs. Cellopenem showed effectiveness against pathogens that are resistant to multiple antibiotics. Now, let's look at some study limitations and considerations. Limitations include, the study was conducted before the implementation of updated treatment guidelines, which may affect its relevance to current clinical practices. The inclusion of ASB in the primary endpoint may not fully align with real world clinical practice patterns. Now, short term follow up limits the ability to assess the long term emergence of resistance. Coming to the key considerations, results indicate that empiric use of ciprofloxacin should be avoided in settings where resistance rates exceed 10%. Now, balancing the therapeutic efficacy with the potential for mild gastrointestinal side effects is essential. So lopinum offers a viable treatment option for multiple drug resistant urinary tract infections addressing a critical gap in current treatment options. Now, finally conclusions and further future directions Solopenum has demonstrated significant efficacy in treating multi drug resistant urinary tract infections, providing a crucial alternative to existing empirical treatment options. Incorporating regional antibiotic resistance data into clinical decision making is essential to optimize therapeutic outcomes. The study highlights sulopenem's potential to minimize bacterial resistance development while maintaining its therapeutic efficacy. There is a critical need to further investigate long term resistance patterns and patient outcomes through comprehensive longitudinal studies. Finally, continued exploration of sulopinem's implementation in diverse clinical settings will help refine its role in managing multi drug resistant infections. Thank you so much for giving me this opportunity and take care, bye.