Pipeline

1 Developed in collaboration with AdaptVac ApS and other partners and out-licensed to Bavarian Nordic.
2 A joint discovery with the University of Copenhagen.
3 A joint discovery project with Evaxion Biotech A/S
COVID-19: ExpreS2ion 2024 estimate based on 2023 market size and CAGR through 2028 from Statista, as of 31 July 2023
Breast Cancer: Global Data, 2022, for HER2+ breast cancer 
Influenza: Fortune Business Insight, Influenza Vaccine market size 2022-2029, 2022 
CMV: Market estimate from Moderna, 41st Annual J.P. Morgan Healthcare Conference (Presentation)

CORONAVIRUS/COVID-19

ExpreS2ion and its associated company AdaptVac have been engaged in the development of a unique capsid virus-like particle (cVLP) COVID-19 vaccine, partly sponsored through a Horizon 2020 EU grant award to the PREVENT-nCoV consortium to rapidly advance the vaccine candidate against COVID-19 into the clinical stage. The candidate vaccine is a cVLP applying ExpreS2-produced SARS-CoV-2 antigens, thereby creating a powerful immunogenic vaccine.

In July 2020, AdaptVac and Bavarian Nordic, a fully integrated biotechnology company focused on the development, manufacture and commercialization of life-saving vaccines, entered into a license agreement providing Bavarian Nordic the global commercialization rights to the proprietary capsid virus like particle-based SARS-CoV-2 subunit vaccine, designated ABNCoV2. For application of our proprietary protein production system ExpreS2, ExpreS2ion and AdaptVac have also entered into a license agreement for this project.

Bavarian Nordic ran a Phase II study to determine the vaccine’s potential as a universal booster. Preliminary results in December 2021 demonstrated a strong boosting effect for all variants tested and confirmed the vaccine’s excellent profile as a non-adjuvanted universal COVID-19 booster vaccine.

Positive Phase II results were presented in February 2022. The full study data confirms that existing levels of SARS-CoV-2 neutralizing antibodies increased by 2-40-fold, depending on the initial levels of antibodies, with no serious adverse events reported. Based on this excellent outcome, Bavarian Nordic initiated a Phase III study in the third quarter of 2022. In October 2022, Bavarian Nordic announced that ABNCoV2 demonstrated durable antibody response six months after vaccination, reflecting a less sharp decline in peak neutralizing titers compared to data published for mRNA vaccines, indicating a potentially longer duration of protection across variants of concern.

In June 2023, Bavarian Nordic published the results of a 12-month follow-up analysis from a subset of subjects enrolled in a Phase II clinical trial of ABNCoV2, which showed high protection levels (>90%) against the original Wuhan strain and previous variants of concern (Beta, Delta, and Omicron BA.4/5). Furthermore, neutralizing antibodies against variant XBB.1.1 were induced in 43% of the subjects at a lower level of efficacy (78%), compared with the original Wuhan strain.

Two weeks later Bavarian Nordic announced that the booster study successfully met its primary endpoint, demonstrating non-inferiority to mRNA-vaccine, and that the regulatory pathway will depend upon the outcome of secondary endpoints, reporting in the third quarter of 2023.

On 31 August 2023, Bavarian Nordic announced that the booster study did not successfully meet its secondary endpoint, in which the goal was to demonstrate protection against the XBB.1.5 variant, and that, due to regulatory authorities’ requirements, the Company saw no commercial opportunity for ABNCoV2 in its current version.

Looking forward, it is essential to highlight the significance of the Phase II 12-month durability data, demonstrating long-term protection, as well as the Phase III primary endpoint data, confirming non-inferiority to Comirnaty, Pfizer/BioNTech's mRNA vaccine. These positive results validate the effectiveness of our ExpreS2 antigen production system and the VLP technology from AdaptVac, respectively. This validation will have a significant impact on how our future vaccine candidates leveraging the same technology platforms are received.

Furthermore, Bavarian Nordic has communicated that their license agreement regarding ABNCoV2 with AdaptVac ApS includes a milestone payment associated with the completion of the Phase III final study report. ExpreS2ion could potentially monetize its 34 percent stake in AdaptVac ApS to extract value from AdaptVac’s proceeds from ABNCoV2 through e.g. dividend pay-out, subject to approval by appropriate parties, including AdaptVac’s board of directors.

BREAST CANCER

Breast cancer is a widespread oncology indication affecting more than 1.3 million people worldwide annually, resulting in more than 450,000 deaths1. The most common treatment today is based on monoclonal antibodies, where the dominating therapies Herceptin (trastuzumab) and Perjeta (pertuzumab) generate annual global sales of USD 7 billion. The target product profile of our lead breast cancer project, ES2B-C001 (HER2-cVLP), is tailored to be highly competitive both in terms of cost and efficacy, thus aiming at a significant market share.

In February 2021, ExpreS2ion signed a patent license agreement with AdaptVac whereby ExpreS2ion exclusively licensed in AV001 (renamed ES2B-C001). This gives ExpreS2ion full control over and responsibility for driving this valuable asset forward, hereby realising the very significant value of this project. At the end of 2021, ExpreS2ion’s candidate demonstrated strong tumour-growth inhibiting effect in a mice models, thus reaching an important pre-clinical milestone ahead of schedule. Additionally, anti-HER2 antibodies from these studies were found to effectively inhibit tumour growth in human cancer cells. The candidate also demonstrated proof-of-concept in HER2-transgenic preventive as well as therapeutic tumour mice models, thus reaching a further important pre-clinical milestone. ExpreS2ion is now completing the preclinical safety studies.

On 17 August 2023, ExpreS2ion announced that the Board had decided to assess strategic options for the ES2B-C001 breast cancer project, aimed at conserving capital resources to further advance the Company’s exploratory vaccine pipeline and technology platforms.  Since that announcement, the Company has been investigating various options for the asset, including finding a development partner to share the cost and upside in the development and Phase I development plans that come at a significantly lower cost than what was previously planned. Further internal development is subject to funding, and non-dilutive funding is currently being prioritized.

INFLUENZA

The MucoVax consortium, a collaboration between ExpreS2ion and University of Copenhagen, has been awarded an Innovation Fund Denmark (IFD) Grand Solutions grant for the development of new platforms for universal mucosal vaccines in a 5-year research project. The award funding covers 71% of the research project and amounts to 29 MDKK (approx. 43 MSEK), of which ExpreS2ion directly is funded with 9.6 MDKK (approx. 14 MSEK). The IFD investment funds 67% of ExpreS2ion’s share of the research project budget.

The aim of the grant is to support the MucoVax consortium in the development of new platforms for universal mucosal vaccines, including performing animal models to test in vivo novel influenza vaccines delivered intranasally. The ambitious aim is to combine ExpreS2ion’s unique ExpreS2 protein production system with the fundamental knowledge in immunology and microbiology of the University of Copenhagen including novel and advanced vaccine platforms.

The MucoVax consortium members are world-leading experts in their respective fields, covering all relevant areas of viral research and vaccine development required for preclinical development of a universal mucosal influenza vaccine. This includes pre-clinical and clinically validated experience from working with malaria pathogens and the SARS-CoV2 corona-virus, applying ExpreS2ion’s Drosophila S2 insect cell expression system, and unique know-how in exploration of adjuvants and virus-like particle (VLP) technologies.

CYTOMEGALOVIRUS

The company has signed a Vaccine Discovery Collaboration Agreement with Evaxion Biotech A/S (NASDAQ: EVAX) for the joint development of a novel cytomegalovirus (CMV) vaccine candidate. The collaboration combines ExpreS2ion’s ExpreS2 platform and resources for vaccine development and production with Evaxion’s proprietary EDEN and RAVENTM artificial intelligence (AI) platforms to design a next generation vaccine candidate that elicit both humoral/antibody and cellular responses.

The aim of the collaboration is to, before the end of 2025, select a novel CMV lead vaccine candidate, which ExpreS2ion has the exclusive right to license under a potential Development and Commercialization Agreement. The research costs and IP licensing for the collaboration project will be divided 50/50 between the parties until 2025, with all costs expected to be covered by each party’s existing budget.

The design and discovery phase of the collaboration will be driven by Evaxion’s proprietary AI platforms, and antigen constructs will be produced by ExpreS2ion in the company’s ExpreS2 platform, followed by assessments in Evaxion’s state-of-the- art in vivo vaccine models.

A potential future Development and Commercialisation Agreement for the jointly discovered CMV lead vaccine candidate is expected to include an upfront payment and future milestone payments to Evaxion from ExpreS2ion not exceeding a six-digit USD amount, as well as sub- licensing royalty to Evaxion from ExpreS2ion based on mid to lower two-digit percentage range of third-party licensee income depending on the clinical development stage of the CMV asset at the time of sublicensing.

 

Note: Legacy programs were set up prior to the Company’s transition into a pipeline-driven biotech company in 2020, and are driven primarily by academic consortia.
Malaria: Data bridge market research, Global Malaria Vaccines Market – Industry trends and Forecast to 2029, 2022
Influenza: Fortune Business Insight, Influenza Vaccine market size 2022-2029, 2022

 

INFLUENZA

The international next-generation influenza vaccine consortium INDIGO, led by the University of Amsterdam with ExpreS2ion as a participating member, is developing a next-generation influenza vaccine in a large collaboration between public and private R&D organisations from the EU, India, and the United States. The project has been awarded a 10 MEUR Horizon 2020 grant from the EU, of which ExpreS2ion’s participation was directly awarded 0.6 MEUR.

The INDIGO consortium plans to carry out the preclinical and clinical development of the project, which contains two novel influenza vaccine concepts, including the application of a novel potent adjuvant by LiteVax BV, the Netherlands, as well as the use of the ExpreS2 platform for antigen production by ExpreS2ion. The aim is to create an influenza vaccine that meets the requirements of global vaccination, i.e. to achieve <10% instead of 60% non-responders, combined with a lower manufacturing cost and better accessibility.

MALARIA PROJECTS

Blood stage (RH5-1)

The University of Oxford is developing the blood-stage Plasmodium falciparum malaria antigen RH5.1 with ExpreS2ion as a collaboration partner. The RH5.1 antigen is produced in ExpreS2ion’s ExpreS2 platform.

A new clinical Phase Ia trial known as BIO-002 is currently being set up in Sheffield, UK, is expected to enroll 24 study participants, and estimated to be completed in late 2024.

A new clinical Phase IIb trial known as VAC091 is also expected to start in 2023 in Burkina Faso. It is currently enrolling 360 study participants and is estimated to be completed sometime in the second half of 2024.

Blood stage (RH5.2-VLP)

With the aim to further improve efficacy, the University of Oxford is developing a second-generation RH5 vaccine, RH5.2, in the ExpreS2 platform. RH5.2 has been engineered to retain regions important for red blood cell recognition, which are targeted by neutralising antibodies. Additionally, the RH5.2 protein will be displayed on the surface of a hepatitis B derived virus-like particle (VLP) in order to maximise the induction of high titre antibodies. The project is funded by the Wellcome Trust.

A new clinical Phase Ib trial known as VAC086 was started in 2023 in The Gambia, is currently enrolling estimated 96 study participants, and is estimated to be completed in the second half of 2025.

Furthermore, a new clinical Phase I/IIa trial known as BIO-001 is currently being set up in Oxford, UK, with 56 planned study participants, and is estimated to be completed in 2025.

Placental (VAR2CSA)

ExpreS2ion has been engaged with malaria research with University of Copenhagen under the so-called PlacMalVac grant consortium, which took place during 2013-18 and led to a publication announced in 2019. University of Copenhagen continues to be engaged with this research, although most recently the research is continuing as a grant-sponsored project without ExpreS2ion’s participation. Antigens are being explored by application of other production systems than ExpreS2, most recently under the so-called ADVANCE-VAC4PM grant consortium which is including the 34% owned associated company AdaptVac. Consequently, ExpreS2ion will not provide further pipeline update on the pregnancy-associated malaria vaccine.

Transmission (Pfs48/45)

The goal for a transmission-blocking vaccine is to prevent the transfer to malaria parasite gametes to mosquitos feeding on persons infected with malaria, thus effectively hindering further spread of the disease. Thereby a transmission-blocking vaccine does not give direct protection from the disease, but it stops the disease from spreading and could therefore lead to eradication of malaria. During the last decade, the inability to produce the full-length Pfs48/45 gamete surface protein antigen has been a major roadblock for researchers aiming to create a transmission-blocking malaria vaccine. However, this challenge was overcome by ExpreS2ion and Jenner Institute at the University of Oxford.

This vaccine is developed by the Horizon 2020-funded OptiMalVax grant consortium, led by the University of Oxford with ExpreS2ion as a member. The objective of the consortium is to create a combination malaria vaccine, and its clinical program will include trials to assess the pre-erythrocytic, blood-stage and mosquito-stage components of the combination vaccine, including this transmission blocking vaccine.

A Phase I trial known as VAC085 is being conducted by Oxford. The vaccinations have been completed and the immunological analysis is ongoing.

Blood stage (RH5.1 + R78C)

A combination vaccine of two proteins (RH5.1 + R78C) started in 2023 a new clinical Phase Ia trial known as VAC089 in Oxford, UK, is currently enrolling an estimated 36 study participants, and is estimated to be completed in second half of 2024.

A new clinical Phase Ib trial known as BIO-003 is currently being set up in Bagamoyo, Tanzania, is expected to enroll 60 study participants, and is estimated to be completed in first half of 2025.

Blood-stage (CyRPA complex)

In 2017, ExpreS2ion and Walter and Eliza Hall Institute of Medical Research (“WEHI”) announced the filing of a joint patent-application on the production of an improved malaria vaccine, see link. Patent applications are pending in Australia and Europe, and there is a granted US patent, which covers a particular sequence of PfRipr in a vector for expression. However, new research data show that combinations of Rh5 with Ripr or CyRPA are the same as each alone. Furthermore, already established data with Rh5 in clinical trials indicate, that pursuing Ripr alone or in combination bears miniscule value compared with the proprietary CyRPA complex concept at the time of the 2017 patent application filing. Consequently, WEHI and ExpreS2ion have decided not to proceed with discovery under the joint patent-application, which is abandoned.