-- Positive Phase 2 (Australia) results strengthen potential best-in-class profile of RSV+hMPV±PIV3 combination vaccines, with the potential differentiated ability to re-vaccinate individuals previously receiving approved RSV vaccines to restore and broaden protection --

-- Robust neutralizing antibody responses across RSV, hMPV and PIV3 in Phase 2 recapitulates Phase 1 results demonstrating best-in-class breadth (with no immune interference) and no drop-off in responses in the oldest participants (75+ years) --

-- Favorable safety & tolerability profile and successful 2,000L commercial-scale production further de-risk late-stage development and commercialization --

Clover Biopharmaceuticals, Ltd. (Clover; HKEX: 02197), a global commercial-stage biotechnology company committed to unleashing the power of innovative vaccines to save lives and improve health around the world, announced positive preliminary data from a Phase 2 clinical trial in older adults in Australia evaluating SCB-1022 (RSV + hMPV) and SCB-1033 (RSV + hMPV + PIV3) protein-based vaccine candidates based on prefusion-stabilized F (PreF)-Trimer subunit vaccine antigens utilizing Clover's validated Trimer-Tag vaccine technology platform.

"We are pleased to announce positive Phase 2 clinical data strengthening the potential first-in-class and best-in-class profile for our RSV+hMPV±PIV3 combination vaccine candidates, with the potential differentiated ability to re-vaccinate individuals previously receiving approved RSV vaccines to restore and broaden protection," said Joshua Liang, Chief Executive Officer & Board Director of Clover. "The positive Phase 2 results significantly de-risk future late-stage development. Importantly, the results also continue to validate our differentiated Trimer-Tag platform for the development of multi-valent protein-based respiratory vaccines that have the potential to make an impact on public health and on chronic diseases caused by respiratory viruses^[1]." 

The ongoing Phase 2 trial for Clover's combination vaccine candidates is a randomized, observer-blinded, multi-center study with 420 older adults (60-85 years) enrolled in Australia, and the participants have been randomized to receive either SCB-1022 (RSV + hMPV), SCB-1033 (RSV + hMPV + PIV3) or placebo.

Immunogenicity

• Antibody titers (geometric mean titers [GMTs]) at 28 days post-vaccination in the Phase 2 were generally in-line with or trended higher than the prior Phase 1 trial.
• Geometric mean fold rises (GMFRs) in neutralizing antibodies (nAbs) at 28 days post-vaccination compared to pre-vaccination:
  • RSV nAbs: Approximately 6-9 fold increases
  • hMPV nAbs: Approximately 6-8 fold increases
  • PIV3 nAbs: Greater than 3 fold increase (approximately 5 fold increase in participants with baseline PIV3 nAbs in the bottom tertile), driven by up to approximately 20 fold increases in PIV3 PreF-specific antibodies^[2]
• No drop-off in antibody responses observed in the oldest participants (75+ years) compared to younger participants (60-74 years).
• No signs of immune interference on RSV and hMPV nAbs from the addition of PIV3 PreF antigen in SCB-1033 (RSV+hMPV+PIV3) compared to SCB-1022 (RSV+hMPV).

Respiratory Tract Infections (Based on AE Reporting)

• Approximately 62% lower rate of respiratory tract infection was observed in the vaccine groups (SCB-1022 and SCB-1033) versus the placebo group within 28 days of vaccination based on AE reporting of any respiratory tract infections (no PCR sequencing of infection cases was conducted in the study).
• Significant RSV outbreak^[3] with co-circulation^[4] of hMPV and PIV in Australia occurred during the study enrollment and follow-up period.

Safety and Reactogenicity

• SCB-1022 and SCB-1033 were generally well-tolerated; solicited local and systemic adverse events (AEs) within 7 days of vaccination were mostly mild and all transient.
  • The most common solicited AEs were fatigue, headache and injection site pain, with mean durations of approximately 2 days for the vaccine groups (SCB-1022 and SCB-1033) and the placebo group. 
• The frequency of unsolicited AEs within 28 days of vaccination was similar across the vaccine and placebo groups.
• There were no vaccine-related serious adverse events (SAEs), AEs of special interest (AESIs), or AEs leading to discontinuation.

Commercial-Scale Manufacturing Scale-Up

• In parallel with the Phase 2 trial, Clover conducted commercial-scale 2,000L bioreactor scale-up production of multiple batches of Trimer-Tagged RSV, hMPV and PIV3 PreF antigen components of SCB-1022/1033.
• The successful 2,000L production process scale-up further de-risk future late-stage development and commercialization.

Based on these positive Phase 2 results for the RSV + hMPV ± PIV3 combination vaccine candidates further validating the Trimer-Tag platform, Clover will continue to evaluate continued mid- and late-stage development plans as well as potential global collaboration opportunities for value maximization.