🔴 Key questions and answers

北美深蓝 OP : Frizer's second-largest holding stock, is this biomedical industry professional investment institution a vegetarian? Could its investment risk control allow the company to bet a large percentage on a single drug's clinical trial? Furthermore, it has been increasing its holdings in the company since 2021/Q4, from 2.4 million to >10 million! Let's take a look at changes in insider positions!
The company also has a seven-valent norovirus vaccine candidate HIL-216, although it is still in its early stages.
Super long venture capital small position, open position!

北美深蓝 OP : —— Can you give some examples where the effectiveness of a vaccine or drug varies greatly among patients of different ages?

Here are some examples of how the effectiveness of a vaccine or drug varies greatly among patients of different ages:

Vaccines
1. **Flu Vaccine**:
- **Children**: The flu vaccine is generally effective in children and can significantly reduce hospitalizations and complications associated with influenza.
- **Elderly people**: The elderly usually respond less well to the influenza vaccine due to decreased immune system function. The vaccine is less effective, but it can still reduce the severity and complications of influenza.

2. **Whooping Cough Vaccine (Tdap) **:
- **Babies**: Whooping cough vaccine is extremely important for infants because pertussis is very fatal to infants, and the vaccine is effective in preventing infection.
- **Adolescents and adults**: Although it also protects adolescents and adults, the pertussis vaccine is less effective in these age groups and symptoms are milder after infection.

3. **Chickenpox Vaccine**:
- **Child**: The chickenpox vaccine is highly effective in children and can prevent most cases of chickenpox.
- **Adults**: For adults who have not been vaccinated and have not had chickenpox, the vaccine is also effective, but may not be as effective as childhood vaccination due to differences in the immune system's response.

Medications
1. **Aspirin**:
- **Adults**: Aspirin is effective in preventing cardiovascular diseases such as heart attacks and strokes in middle-aged and elderly people, especially those at high risk of cardiovascular disease.
- **Children**: Aspirin use in children can cause serious side effects, such as Reye's syndrome, so aspirin is not recommended for children.

2. **Statins**:
- **Adult**: Statins are widely used to lower cholesterol and prevent cardiovascular disease, and are particularly effective in middle-aged and elderly patients.
- **Children**: Generally not recommended for children unless they have specific diseases such as familial hypercholesterolemia, and their long-term safety and efficacy still require further research in children.

3. **azithromycin**:
- **Adults**: Azithromycin is very effective in treating bacterial infections such as pneumonia and bronchitis in adults.
- **Children**: Although also used in children, it may be as effective or worse as other antibiotics in treating certain conditions, such as ear infections, and may have different side effects.

These examples show that patients of different ages may respond significantly to vaccines and medications, so the age and specific health conditions of patients need to be considered when formulating treatment plans.

北美深蓝 OP : HilleVax's technology platform mainly focuses on developing norovirus vaccines, especially its main candidate vaccine HIL-214. HillEvax uses virus-like particle (VLPS) technology, which is a method that has received much attention in vaccine development in recent years. The following is an introduction to the features of this technology platform and its advantages and disadvantages:

### Technical Platform Features

1. **Virus-like particles (VLPs) **: Hillevax's technology platform uses VLPs to simulate the structure of noroviruses, but these particles do not contain the virus's genetic material and therefore do not cause infection. VLPs can trigger a strong immune response, similar to natural viral infections, but there is no actual viral risk.

2. **Polyvalent Vaccine**: HIL-214 is a bivalent vaccine against norovirus, containing the two main norovirus strains GI.1 and GII.4. This multivalent vaccine is designed to provide broader protection, covering a wider range of norovirus variants.

3. **Focus on enterovirus**: The platform mainly targets norovirus, which causes acute gastroenteritis, which is one of the leading causes of acute gastroenteritis globally, particularly in children and the elderly.

### Advantages

1. **Strong immunogenicity**: VLPs can effectively simulate the structure of the virus, induce a strong immune response, and avoid the risk of actual infection.

2. **High safety**: Since VLPs do not contain the genetic material of the virus, they do not replicate or cause infections, reducing safety risks after vaccination.

3. **Potential wide applications**: VLP technology is not only suitable for norovirus vaccines, but can also be extended to other viruses, such as human papillomavirus (HPV) and hepatitis B virus (HBV), and has been successful in these fields.

4. **Multivalent protection**: By including multiple virus strains, HIL-214 aims to provide a wider range of protection, which is expected to cover multiple norovirus variants and reduce the incidence of acute gastroenteritis.

### Disadvantages

1. **Clinical trial risk**: As shown by recent clinical trial failures, although it has shown potential in earlier studies, it is challenging to prove its effectiveness in large-scale clinical trials, and may face problems where effectiveness is not as good as expected.

2. **Production Complexity**: The production process for VLPs is complex and involves expensive biotechnological manufacturing processes, which may affect vaccine affordability and supply chain management.

3. **Immune persistence uncertain**: Although VLPs can induce a strong immune response, their long-term immunoprotective effect (persistence) still needs further verification.

4. **Effectiveness against mutants**: Norovirus is highly mutated, and new variants may evade the protection of existing vaccines, causing vaccines to be updated and re-evaluated regularly.

### Conclusions

The HiLeVax technology platform is based on virus-like particle technology and has the advantages of high immunogenicity and safety, but it also faces challenges such as clinical trial risks and production complexity. Although recent clinical trial results of HIL-214 fell short of expectations, HilleVax has the potential to succeed in other fields by improving and expanding its technology platform.

北美深蓝 OP : HillEvax said it will explore the potential to continue developing HIL-214 and another vaccine candidate, HIL-216, for adults.

北美深蓝 OP : Norovirus has become the leading cause of gastroenteritis in middle- and high-income countries and resource-poor regions around the world. Those most likely to develop serious illnesses include young children, the elderly, and immunocompromised people. Norovirus is highly infectious, highly resistant to environmental conditions, and has multiple transmission routes, including human-to-human transmission, foodborne transmission, and contaminated surfaces. Norovirus can cause acute, mild to severe illness characterized by vomiting, diarrhea, fever, dehydration, and abdominal pain, putting a heavy burden on public health. The clinical picture is similar in adults and older children. Although deaths of children from acute gastroenteritis (AGE) due to norovirus are rare in industrialized countries, it is more common in developing countries. Although this may be the reason young children are hospitalized, there are fewer cases in the first 6 months after birth, which may be due to the protective effects of maternal antibodies against placental transmission and breast milk. Additionally, norovirus infections have significant socioeconomic impacts on hospitals, schools, daycare centers, and other closed environments. With the successful implementation of rotavirus vaccination programs for infants, the burden of rotavirus infection in children has been reduced, and norovirus infection is increasingly recognized as the main cause of AGE in many countries around the world.

北美深蓝 OP :
“We are disappointed that the NEST-IN1 study did not meet its primary efficacy endpoint,” said Rob Hershberg, MD, PhD, Chairman and Chief Executive Officer of HilleVax. “While HIL-214 previously showed clinical benefit in adults, NEST-IN1 was the first efficacy study conducted in infants for a norovirus vaccine candidate. We believe the efficacy in the infant setting may have been impacted by the appearance of multiple emerging GII.4 strains in this trial.”

“We sincerely thank the trial investigators, clinical sites and the HilleVax team for conducting a highly rigorous study, and we are deeply appreciative to the infants and families that participated in this trial,” said Dr. Hershberg.

The NEST-IN1 study was conducted after a Phase 2b study in adults, NOR-211, demonstrated statistically significant efficacy against moderate or severe AGE due to norovirus. The company plans to discontinue further development of HIL-214 in infants and is exploring the potential for continued development of HIL-214 and HIL-216, HilleVax’s Phase 1 ready vaccine candidate, in adults.