Hillevax's Norovirus Vaccine Market Challenges and Strategies

As of July 8, 2024, Hillevax's market capitalization has dropped to $1,000,000, following the company's announcement that its bivalent norovirus vaccine, HIL-218, did not achieve the primary endpoint in preventing acute gastroenteritis in the NEST-IN1 Phase 2b infant trial. This revelation has created uncertainty in the market about Hillevax's research and development capabilities. To counteract this setback, Hillevax is focusing on expanding its pipeline in China.

In January 2024, HilleVax entered into an exclusive licensing agreement with Chengdu Kanhua Bio. This agreement grants HilleVax the global rights, excluding China, Hong Kong, Macau, and Taiwan, to develop, produce, and commercialize Kanhua Bio's recombinant hexavalent norovirus vaccine, HIL-216, along with its derivatives. As part of the deal, Kanhua Bio received an upfront payment of $15,000,000 and stands to gain up to $255,500,000 in milestone payments subject to specific development and sales milestones being met. Furthermore, Kanhua Bio is eligible for a single-digit percentage royalty on net sales in the territories covered by the agreement.

HIL-216, a hexavalent norovirus vaccine created by Kanhua Bio using genetic engineering, is based on virus-like particles (VLPs) and targets six major circulating norovirus genotypes: GI.1, GII.2, GII.3, GII.4, GII.6, and GII.17. This vaccine is theoretically capable of preventing over 90% of norovirus infections and acute gastroenteritis. HIL-216 received clinical trial authorization in Australia and the United States in February and September 2023, respectively, but has not yet received clinical trial approval in mainland China. It is the world's first and only hexavalent norovirus vaccine to have received clinical trial authorization. The company plans to initiate a Phase 1 clinical trial for HIL-216 in 2024.

In addition to collaborating with Kanhua Bio, HilleVax's pipeline also includes the bivalent norovirus vaccine HIL-214, formerly known as TAK-214 under Takeda's development. HilleVax was granted exclusive global development and commercialization rights for HIL-214, excluding Japan, where Takeda retained commercialization rights.

HIL-214 is a VLP-based bivalent vaccine designed to cover GI.1 and GII.4 strains, which are the primary causes of human gastroenteritis. This vaccine aims to prevent moderate to severe acute gastroenteritis (AGE) caused by norovirus infections. Although norovirus has seven known genogroups, genogroups I and II account for most human cases, with GII.4 strains being the major drivers of human outbreaks, often leading to more severe illness with higher mortality rates.

In May 2022, HilleVax initiated the NEST-IN1 Phase 2b clinical trial, a randomized, double-blind, placebo-controlled study to evaluate the safety, immunogenicity, and efficacy of HIL-214 in approximately five-month-old infants. In December 2022, interim data from the first 203 participants indicated that HIL-214 elicited strong immune responses 28 days after the second dose. Geometric mean titers (GMTs) of pan-Ig antibodies were significantly higher in the HIL-214 group compared to the placebo group, with figures reaching 11,102.0 IU/mL for GI.1 and 2,185.5 IU/mL for GII.4. These results represented an over 18-fold increase in geometric mean fold rise (GMFR) from baseline. Additionally, serum antibody response rates (SRRs) were 99.0% and 86.9% for GI.1 and GII.4, respectively, compared to 4.1% and 3.1% in the placebo group. By April 2023, HilleVax had completed the enrollment of over 3,000 participants in the NEST-IN1 trial, with top-line data expected in mid-2024.

As HilleVax advances the pediatric registration for HIL-214, the company is also seeking approvals for the vaccine in other age groups. In the third quarter of 2023, HilleVax initiated three additional clinical trials to support the progress of HIL-214. These include NOR-109, a Phase 1 trial in Japanese infants; NOR-206, a Phase 2 trial evaluating the co-administration of HIL-214 with other standard infant vaccines; and NOR-212, a Phase 2 trial assessing the safety and immunogenicity of HIL-214 in older adults.