MinervaX investment analysis

October 17, 2023

This is not investment advice. We used AI and automated software tools for most of this research. We did some fact checking but cannot guarantee the accuracy of everything in the article. We do not have a position in or a relationship with the company.

Overview

MinervaX is developing a maternal vaccine for the prevention of adverse pregnancy outcomes and life-threating infections caused by Group B streptococcus (GBS).

GBS is a bacteria that colonizes some 20% of pregnant women. GBS is the leading cause of life-threatening infections in newborns in the first 3 months of life, causing an estimated 320,000 cases of neonatal invasive disease, 60,000 stillbirths, 3,500,000 preterm deliveries, and 10,000 babies suffering from long-term neurological damage annually world-wide.

Current countermeasures primarily include administering large amounts of prophylactic antibiotics to pregnant women. This contributes to emerging antibiotic resistance as well as potential negative impacts on neonatal development.

MinervaX's vaccine is designed to be generally effective, covering close to 100% of clinical GBS isolates, and drives an antibody response that transfers from mother to child, potentially protecting against GBS disease in newborns. It is intended to be administered universally to pregnant women.

The vaccine is a protein-only vaccine derived from bacterial antigens from the alpha-like surface proteins family of GBS. This approach is potentially superior to existing GBS vaccine candidates that predominantly rely on traditional capsular polysaccharide (CPS) conjugate technology.

The vaccine is in Phase II development. Phase I trials in 240 healthy adults and 60 healthy women showed promising safety profiles and effective antibody response. In the Phase 2 study, clinical study data from 200 pregnant women from South Africa and Uganda is being compiled. Of these, over 140 babies have already been born.

Another study has commenced in Denmark and the UK involving 270 healthy pregnant women.

MinervaX Pipeline Overview

Product name	Modality	Target	Indication	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA submission	Commercial
GBS Maternal	Vaccine	Group B streptococcal vaccine	Prevention of GBS infection in newborns
GBS Adult	Vaccine	Group B streptococcal vaccine	Prevention of GBS infection in older adults

The company raised a EUR 54M funding round in October 2023. The round was led by EQT Life Sciences and Orbimed, along with existing investors Novo Holdings, Pureos Ventures, Sanofi Ventures, Trill Impact Ventures, Adjuvant Capital, Wellington Partners, Industrifonden, Sunstone LifeScience Ventures, and LF Invest.

Highlights and risks

Valuation

Contact us for valuation analysis.

Pipeline analysis

Scientific thesis

MinervaX's vaccine formulation is built on bacterial antigens sourced from the alpha-like surface proteins of Group B Streptococcus (GBS). These antigens, derived from the N-terminal domains of the predominant alpha-like protein serotypes, ensure coverage for almost all clinical GBS isolates, offering comprehensive protection against a broad spectrum of GBS strains.

Unlike many GBS vaccine candidates that rely on traditional capsular polysaccharide (CPS) conjugate technology, MinervaX's innovative protein-only approach, coupled with AlOH adjuvant (a common vaccine adjuvant that enhances the immune response and potentially reduces dosing frequency and size), promises enhanced efficacy and possibly fewer side effects. Potential benefits of MinervaX's approach include:

• Broader Coverage: Traditional CPS vaccines are often based on the polysaccharide capsule surrounding bacteria. However, bacteria may have multiple capsular types, leading to the need for a multivalent vaccine to cover various strains. MinervaX's vaccine targets the N-terminal domains of the most prevalent alpha-like protein serotypes, ensuring coverage for almost all clinical GBS isolates. This broad-spectrum approach offers protection against a wider range of GBS strains than a CPS-based vaccine might.
• Stable Antigenic Targets: Polysaccharide capsules can be subject to antigenic variation, which means the bacterial surface structures might change over time. Proteins, especially conserved ones like the alpha-like surface proteins targeted by MinervaX, are typically more stable antigenic targets. This can lead to a more consistent and lasting immune response.
• T-Cell Immunity: Protein-based vaccines, compared to polysaccharide-based vaccines, have a better capability to stimulate T-cell responses. This is important because T-cells play a crucial role in the overall immune response, especially in memory recall and providing long-term immunity.
• Conjugation Limitations: CPS vaccines are often conjugated to a protein carrier to boost their immunogenicity. This conjugation process can be complex, and the resulting conjugated vaccine might have variability from batch to batch. A protein-only vaccine eliminates the need for this additional step and its associated challenges.
• Potential for Fewer Side Effects: Protein-only vaccines might have a more favorable safety profile. The absence of polysaccharides, which can sometimes lead to unintended immune reactions, might result in fewer side effects.
• Cost and Manufacturing: Protein-based vaccines might be simpler and more cost-effective to produce at scale compared to conjugated CPS vaccines, given the complexities associated with the conjugation process.

GBS-NN Maternal vaccine

GBS is a known cause of several adverse pregnancy outcomes and serious neonatal infections globally. A successful GBS vaccine could provide substantial therapeutic benefits and have public health implications. MinervaX's approach is based on a solid scientific foundation and encouraging clinical data, presenting a potential solution to this global health issue.

Overview of GBS

Group B Streptococcal (GBS) is a prominent pathogen responsible for life-threatening infections in newborns. Depending on the region, GBS affects 0.5-2 out of every 1,000 newborns and is responsible for half of all life-threatening infections in this population. Annual global figures indicate approximately 320,000 neonatal invasive disease cases, 60,000 stillbirths, 3.5 million preterm deliveries, and 10,000 infants enduring long-term neurological damage due to GBS.

Between 15-25% of women may carry GBS at any time, with the potential risk of transmitting it to their fetus in utero, during childbirth, or in the early months postpartum. GBS colonization in pregnant women can lead to severe outcomes, such as premature births, stillbirths, and life-threatening infections in newborns like sepsis, pneumonia, and meningitis. These infections can culminate in severe morbidity, permanent disability, or even death.

A prevalent GBS intervention is intra-partum antibiotic prophylaxis (IAP), administered to women colonized with GBS late in pregnancy or those at elevated risk of passing the bacteria to the newborn during childbirth. Introduced in 2000, IAP reduced the incidence of Early Onset Disease (EOD) – which occurs within the first six days of life – by approximately 80%. Despite its success, IAP has notable shortcomings:

• It doesn't affect GBS-triggered late abortions, stillbirths, or premature births.
• It doesn't impact Late Onset Disease, which appears between 7 days to 3 months of age, and carries the highest meningitis burden. Half of the infants recovering from GBS meningitis experience long-term sequelae, such as brain damage, hearing loss, blindness, and severe learning challenges.
• Its use is confined to high-income nations, leaving low-income countries without access.
• The effectiveness of IAP is jeopardized by the rising antibiotic resistance seen in GBS, especially against widely-used antibiotics like penicillin.
• Broad-spectrum antibiotic use may detrimentally influence the infant's developing intestinal microbiome, escalating risks for conditions like asthma, ADHD, and learning disabilities.

An effective GBS vaccine targeting maternal immunization could offset the gaps in the current intervention methods. Potential advantages include:

• Shielding pregnant women from GBS-induced adverse outcomes, such as late abortions, stillbirths, and premature deliveries.
• Providing passive immunity to the fetus against in utero GBS infections.
• Protecting the infant from GBS infections during the vulnerable first three months of life.
• Reducing reliance on prophylactic antibiotics, curtailing the rise of antibiotic-resistant bacteria, and fostering healthier neonatal microbiome development.

Supporting evidence and therapeutic rationale

MinervaX's vaccine formulation is built on bacterial antigens sourced from the alpha-like surface proteins of Group B Streptococcus (GBS). These antigens, derived from the N-terminal domains of the predominant alpha-like protein serotypes, ensure coverage for almost all clinical GBS isolates, offering comprehensive protection against a broad spectrum of GBS strains.

Most individuals already possess naturally occurring antibodies against the vaccine's antigens, which arise from early-life bacterial colonization. These IgG1 antibodies, known to actively transfer from mother to fetus, are present at even higher levels in the infant (up to 120% compared to the mother). Such antibodies have been associated with protection against invasive GBS diseases in infants, offering a foundation upon which the vaccine can amplify protective responses.

The GBS-NN component of the vaccine has demonstrated significant efficacy in several animal models, including passive and active immunization, as well as neonatal protection models. These results solidify the potential effectiveness of the vaccine in preventing lethal GBS infections.

Phase 1 study results

The trial was a randomized, double-blind, placebo-controlled, phase I study involving healthy, non-pregnant women.

An initial dose-escalation phase involved administering two doses, four weeks apart, of 10, 50, or 250 µg of GBS-NN, either with or without an aluminium hydroxide adjuvant (n = 60).

A subsequent dose-confirmation phase compared a single dose of 100 µg adjuvanted GBS-NN to two doses (given four weeks apart) of either 50 or 100 µg adjuvanted GBS-NN (n = 180).

Safety and the immune response were monitored for one year.

Initial human trials involving the GBS-NN component alone have confirmed the vaccine's safety, with results on par with other AlOH-adjuvanted protein-based vaccines. Furthermore, the vaccine induced robust, enduring, functionally active antibodies that can thwart GBS invasion into epithelial cells and eliminate GBS through opsono-phagocytosis. The combined GBS-NN & GBS-NN2 has also showcased comparable safety and efficacy:

• The GBS-NN vaccine was generally well tolerated. Most side effects were mild and related to the injection site.
• Using the adjuvant notably enhanced the antibody concentrations.
• A second dose further boosted the immune response.
• Throughout the one-year study, the antibody levels (IgG GMCs) remained significantly elevated.
• The most effective regimen was two 50 µg doses, which resulted in an IgG GMC of 16.9 µg/ml twelve weeks after the first dose. Under this regimen, all subjects achieved antibody levels exceeding 1 µg/ml, with 89% surpassing 4 µg/ml.
• The second dose had the most beneficial impact on subjects who initially had IgG levels below the median for the whole group.
• Correlates derived from initial studies provide a benchmark indicating the levels of vaccine-induced antibodies necessary to grant protection. These correlates further reinforce the vaccine's potential, as 100% of vaccinated participants in the Phase I trial met these protective thresholds.

Phase 2 program overview

A Phase 2 study has started in Denmark and the UK with 270 healthy pregnant women under an IND. The study is a randomized, placebo-controlled study with five treatment groups.

Three treatment groups receive two doses of the vaccine and one placebo (with the placebo as the first, second or third dose). One group receives one vaccine dose and two placebos. One group gets three placebo doses. Injections are given at 22, 26, and 30 weeks gestational age.

Endpoints:

• Mothers and babies are followed up to delivery and then at 28, 90, and 180 days post-delivery.
• Primary endpoint: Concentrations of IgG antibodies specific to AlpN proteins in baby's cord blood at delivery.
• Selected secondary endpoints:
• Mother's side effects like injection site reactions and other adverse events up to day 84.
• Mother's clinically significant changes in vital signs, physical examination, and lab tests up to day 84.
• Baby's measures including gestational weight, weight, length, head circumference, and Apgar score (a quick health test for newborns) at various points from delivery to 180 days.
• Baby's developmental milestones using the Ages & Stages questionnaire at 6 months.
• Concentrations of specific IgG antibodies in both mother's blood at delivery and baby's blood at 1 and 3 months.
• Opsonophagocytic killing assay (OPKA) titres in cord and maternal blood at delivery
• Concentrations of IgG antibodies specific to the NN and NN2 fusion proteins in maternal blood
• Concentrations of IgG and IgA antibodies specific to the AlpN proteins in colostrum and in breast milk

The Phase 2 program is expected to complete in late 2023, with Phase 3 potentially beginning in 2024.

Development risks

• Population Differences:
• The Phase 1 study involved non-pregnant women, while Phase 2 is conducted on pregnant women. The physiological differences between pregnant and non-pregnant women may affect the vaccine's safety profile and efficacy. Hence, extrapolating Phase 1 results to a pregnant population could be a risk.
• Potential for Enhanced Disease:
• In some vaccine developments for other pathogens, vaccination has inadvertently led to enhanced disease upon exposure to the actual pathogen. It's crucial to monitor for any signs of enhanced susceptibility or severity of GBS infections in vaccinated individuals.
• Maternal to Child Transmission:
• While the vaccine aims to protect newborns by vaccinating mothers, it's possible that it may not entirely prevent maternal-to-child transmission of GBS, especially if protection wanes towards the end of pregnancy when transmission risk is highest.
• Adjuvant Use:
• The use of an aluminium hydroxide adjuvant in Phase 1 showed enhanced immunogenicity. However, it's essential to monitor for potential adverse reactions specifically related to the adjuvant, especially in pregnant women and the potential effects on the fetus.
• Immunological Considerations:
• It's encouraging that a second dose further boosted the immune response in Phase 1. However, it's essential to ensure that high antibody levels directly correlate with protection against neonatal GBS-related issues.
• General Vaccine Development Risks:
• Like any vaccine development, there are risks of unexpected adverse events, manufacturing challenges, and regulatory hurdles. These can impact the timeline and success of bringing the vaccine to market.

Market opportunity

GBS poses significant risks to newborns, leading to severe infections, stillbirth, and preterm delivery. The development of a vaccine against GBS could have substantial market potential, especially when compared with other vaccines for maternal or infant indications.

A useful comparison might be the pneumococcal conjugate vaccine (PCV) such as Prevnar 13, which is used to prevent disease caused by Streptococcus pneumoniae in both children and adults. At its peak, Prevnar 13 generated annual revenues of over $5 billion for Pfizer. This vaccine addresses a broad population, as it's recommended for children and adults over 50 in many countries.

Revenue build

The primary target for a GBS vaccine would be pregnant women, as maternal immunization could protect newborns. Every year, there are approximately 140 million births globally. Assuming the vaccine is accessible globally, this number would be the maximum potential patient pool per year.

Not all countries or individuals would have immediate access to or accept the vaccine. Let's assume that in the first few years post-launch, the vaccine reaches 10% of the global pregnant population, i.e., 14 million women.

Pricing can vary based on regions: High-income countries might price the vaccine higher, while low and middle-income countries, through global alliances like GAVI, could get it at subsidized rates. For simplicity, let's estimate an average global price of $50 per dose, with two doses required (as indicated by the Phase 1 results), resulting in $100 per patient.

Based on the above, potential revenue in the first few years could be: 14 million women x $100 = $1.4 billion.

The potential introduction of competing vaccines or other preventative measures could impact market share. Large pharma companies like GSK and Pfizer, with extensive experience developing and commercializing vaccines, are developing GBS vaccines, and many smaller groups are also developing programs. The duration of protection the vaccine offers would determine if booster shots are needed and how frequently, impacting long-term revenue projections.

The vaccine is also being studied in older adults, who are vulnerable to severe GBS-induced disease including sepsis, pneumonia, cellulitis and soft tissue infections. This could further increase the revenue potential. The vaccine is currently being studied in a Phase 1 study in 90 older patients.

Commercial considerations

Not all vaccines gain immediate global approval. A vaccine might first be approved in countries where clinical trials were conducted or where the regulatory pathway is more streamlined. Early on, the manufacturer might face constraints in producing enough doses for global distribution.

For a GBS vaccine, considering its potential to prevent severe outcomes in newborns, there might be strong impetus from health agencies to ensure rapid adoption, but exact figures would be speculative without more specific data.

The rate of uptake for a new vaccine varies based on multiple factors, and each vaccine's trajectory can be different. For context, here are some examples of launches of comparable vaccines:

• HPV Vaccine (Gardasil and Cervarix): The uptake of the HPV vaccine varied widely among countries. In places like the UK and Australia, the rapid adoption was facilitated by national immunization programs, achieving over 70% coverage in target groups within a few years. In contrast, in some other countries, adoption was slower due to various reasons ranging from public controversies to logistic challenges. Gardasil and Cervarix were priced at about $130 to $150 per dose in the U.S. market, but again, prices varied widely in global markets.
• Prevnar 13: The uptake of Prevnar (both the original and its subsequent version, Prevnar 13) was facilitated by the inclusion in national immunization schedules, particularly in developed countries. In the U.S., for example, it achieved high coverage rates (over 80% for the recommended series) within a few years of its introduction. However, global coverage took longer, especially in lower-income countries, where the introduction was sometimes staggered over years and facilitated by groups like GAVI. In the U.S., Prevnar 13 was priced at over $200 per dose for the private market, but bulk purchases by government programs and in other countries, especially low-income ones, received significant discounts.
• Rotavirus Vaccines (Rotarix and Rotateq): These vaccines, introduced in the late 2000s, also saw varied uptake. By 2015, while many developed countries had incorporated them into national schedules, global coverage was still below 30%. This was partly because many countries, especially in Asia and Africa, had not yet introduced the vaccine. In lower-income countries supported by GAVI, Rotarix and Rotateq were available for as low as $2-3 per dose, while in the U.S., the private market price was over $100 per dose.

Funding history

• Equity Financing, 15th February 2016:
• Amount: DKK 16 million (EUR 2.2 million)
• Investors: Novo Seeds (lead), Sunstone Capital, LF Investment
• Pipeline at funding: Not explicitly mentioned in the snippet provided, but since it's an early round of funding, it can be inferred that the company was in the pre-clinical or very early clinical phase of development for its GBS vaccine.
• Series A, 8th January 2019
• Amount: 3.6 mEUR from Novo Holdings REPAIR Impact Fund + 0.8 mEUR from Sunstone Life Science Ventures = 4.4 mEUR total
• Investors: Novo Holdings REPAIR Impact Fund, Sunstone Life Science Ventures
• Pipeline at funding: Completion of an initial Phase I trial in 240 healthy adult women with positive results. Funding aimed to finalize Phase I development, with plans to expand coverage by adding a second vaccine component. The clinical trial initiated in the UK on January 8, 2019.
• Series B, 15 December 2020
• Amount: EUR 47.4 million (USD 57M)
• Investors: New investors - Sanofi Ventures, Wellington Partners, Adjuvant Capital, and Industrifonden. Existing investors - Novo Holdings REPAIR Impact Fund, Sunstone Life Science Ventures, LF Investment
• Pipeline at funding: Completion of Phase I studies across 300 healthy female subjects. The funds would advance the GBS vaccine through Phase II clinical trials and support preparations for Phase III, including manufacturing and regulatory aspects.
• Equity + loan, 15 December 2022
• Amount: 72 million EUR (22 million EUR equity financing + 50 million EUR loan facility from European Investment Bank)
• Investors: New investors - Trill Impact Ventures, Pureos Bioventures. Existing investors - REPAIR Impact Fund (Novo Holdings), Sunstone Life Science Ventures, LF Investment, Wellington Partners, Sanofi Ventures, Adjuvant Capital, and Industrifonden
• Pipeline at funding: Initiation of enrollment of pregnant women in its Phase 2 clinical trial in multiple countries and completion of dosing of healthy adult women in a Phase 1 booster clinical trial in the UK.
• Equity funding, 11 October 2023
• Amount: 54 million EUR
• Investors: New investors - EQT Life Sciences, OrbiMed. Existing investors - Novo Holdings, Pureos Ventures, Sanofi Ventures, Trill Impact Ventures, Adjuvant Capital, Wellington Partners, Industrifonden, Sunstone LifeScience Ventures, and LF Invest
• Pipeline at funding: Progressing two Phase II clinical trials in 470 pregnant persons across multiple countries. Initial data is positive, with the vaccine showing an acceptable safety profile and inducing functionally active antibodies. The company is also pursuing Phase I development for older adults.