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Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced that updated results from the ongoing pivotal

Phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial of its dengue vaccine candidate (TAK-003) were presented at the American Society of Tropical Medicine and Hygiene (ASTMH) 68th Annual Meeting. The data presented include an update on overall vaccine efficacy (VE) and a formal assessment of secondary efficacy endpoints by serotype, baseline serostatus and disease severity (18 months after the second dose, which was administered three months after the first dose). The TIDES trial met all secondary endpoints for which there were a sufficient number of cases. Overall vaccine efficacy and safety results from the second part of the study were generally consistent with the data reported in the primary endpoint analysis (overall VE was 73.3% [95% confidence interval (CI): 66.5% to 78.8%; p<0.001] in the 18-month analysis, and VE was 80.2% (95% CI: 73.3% to 85.3%) in the primary endpoint analysis [12 months after the second dose]). The primary endpoint analysis of overall VE was recently published in the New England Journal of Medicine,[i] demonstrating protection against virologically-confirmed dengue (VCD) in children ages four to 16 years, regardless of previous exposure to dengue.

Assessment of secondary endpoints showed that VE against hospitalized dengue was 90.4% (95% CI: 82.6% to 94.7%; p<0.001) and VE against dengue hemorrhagic fever was 85.9% (95% CI: 31.9% to 97.1%); efficacy against severe VCD could not be determined due to an insufficient number of cases (VE: 2.3% [95% CI: -977.5% to 91.1%). Overall efficacy was similar in baseline seropositive and seronegative individuals (VE: 76.1% [95% CI: 68.5% to 81.9%] vs. VE: 66.2% [95% CI: 49.1% to 77.5%], respectively). Efficacy results varied by individual serotype: VE was 69.8% for dengue serotype 1 (95% CI: 54.8% to 79.9%), 95.1% for dengue serotype 2 (95% CI: 89.9% to 97.6%), and 48.9% for dengue serotype 3 (95% CI: 27.2% to 64.1%). There were an insufficient number of dengue serotype 4 cases to adequately assess efficacy at this time (VE: 51.0% [95% CI: -69.4% to 85.8%]). Efficacy endpoints will continue to be assessed over the course of the trial.

Analyses of exploratory endpoints in VCD showed similar VE among seropositive and seronegative individuals for dengue serotype 1 (VE: 72.0% [95% CI: 52.2% to 83.6%] vs. VE: 67.8% [95% CI: 40.3% to 82.6%]) and dengue serotype 2 (VE: 93.7% [95% CI: 86.1% to 97.1%] vs. VE: 98.1% [95% CI: 85.8% to 99.7%]). For dengue serotype 3, VE in seropositive individuals was 61.8% (95% CI: 43.0% to 74.4%), and

-68.2% (95% CI: -318.9% to 32.4%) in seronegative individuals. The VE against dengue serotype 3 in seronegative individuals was statistically inconclusive but suggests a lack of efficacy. Efficacy against dengue serotype 4 could not be determined due to a limited number of cases. Planned follow-up will further characterize the performance of the vaccine candidate in dengue serotypes 3 and 4.

Consistent with previous results, Takeda’s dengue vaccine candidate was generally well tolerated, and there have been no important safety risks observed to date.

“The 18-month data presented at ASTMH further our understanding of the efficacy and safety of Takeda’s dengue vaccine candidate,” said Shibadas Biswal, M.D., Medical Director, Dengue Clinical Development, Takeda, who presented the TIDES data at ASTMH. “These results are encouraging, and we’re particularly pleased to see the consistency in overall efficacy as compared to our 12-month analysis, as well as the overall efficacy in seronegative participants. While additional data is needed to fully understand the profile of TAK-003, particularly against serotype 3 in seronegatives, we see its potential to address key priorities for dengue control, including protection of seronegative populations and prevention of hospitalization.”

The Phase 3 TIDES trial is ongoing and will continue to assess safety and efficacy of the vaccine candidate in study subjects for a total of four and a half years. Takeda’s dengue vaccine candidate is not currently licensed anywhere in the world.

In total, Takeda presented two oral and nine poster presentations at ASTMH, including data for its Zika vaccine candidate from ZIK-101, a randomized, placebo-controlled, double-blind Phase 1 trial designed to evaluate the safety and immunogenicity of the investigational vaccine candidate in 240 male and female subjects between the ages of 18 and 49.[ii] The Phase 1 trial also assessed different dose levels to support the progression of the vaccine candidate into future studies.2 Takeda’s Zika program is supported by federal funds from Biomedical Advanced Research and Development Authority (BARDA), within the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services.

[i] Biswal S, et al. Efficacy of a tetravalent dengue vaccine in healthy children and adolescents. N Engl J Med. 2019; Retrieved November 2019.

[ii] ClinicalTrials.gov. Safety, Immunogenicity and Dose Ranging Study of Inactivated Zika Virus Vaccine in Healthy Adult Participants. 2019. Retrieved November 2019.