ES2B C001
Alternative Names: AV-001 - AdaptVac; ES2B-C001; ES2B-C001 (HER2-cVLP)Latest Information Update: 21 Apr 2023
At a glance
- Originator AdaptVac
- Class Antineoplastics; Cancer vaccines; Immunotherapies; Virus-like particle vaccines
- Mechanism of Action Immunostimulants
-
Orphan Drug Status
No
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity No
Highest Development Phases
- Preclinical HER2 positive breast cancer
Most Recent Events
- 18 Apr 2023 Pharmacodynamics data from a preclinical study in Breast cancer released by ExpreS2ion Biotechnologies
- 14 Apr 2023 Pharmacodynamics and immunogenicity data from preclinical trial in HER2-positive-breast-cancer presented at the 114th Annual Meeting of the American Association for Cancer Research (AACR-2023)
- 23 Jan 2023 ES2B C001 is still in preclinical phase for HER2-positive breast cancer in USA (AdaptVac pipeline; January 2023)
Development Overview
Introduction
ES2B C001 (previously known as AV 001) is a vaccine being developed by AdaptVac (joint-venture between ExpreS2ion Biotechnologies and NextGen Vaccines,a spin-out of the University of Copenhagen) for the treatment of cancer including HER2-positive breast cancer. AdaptVac uses combination of ExpreS2ion Biotechnologies' proprietary ExpreS2 technology platform and a proprietary virus-like particle (VLP) technology of the University of Copenhagen. ES2B C001 activates the Tie2 receptor and restore normal barrier defense in the vasculature. Preclinical development is ongoing in USA.
ExpreS2 platform is a non-viral insect cell expression system that establishes stable polyclonal pools that provide high protein expression levels without selection pressure. The system is designed for transient or stable transfections using vector DNA containing a very strong proprietary hybrid promoter. The virus-like particle (VLP) technology employs VLPs which are enabled to bind efficiently to various vaccine antigens via a genetically engineered binding-tag on the VLP surface. The company utilises the split-protein conjugation system to generate stable isopeptide bound antigen-VLP complexes by simply mixing of the antigen and VLP components.
Company Agreements
In February 2021, ExpreS2 ion Biotechnologies exclusively in licensed ES2B C001 (AV 001) from AdaptVac. Under the terms of agreement ExpreS2 ion Biotechnologies will pay an upfront payment of DKK 2.5 million upon signing, followed by aggregated milestone based payments of DKK 215 million during development and marketing approval, and a lower single digit percentage royalty based on net sales. Earlier in February 2020, AdaptVac signed an option to license agreement with ExpreS2 ion Biotechnologies, whereby ExpreS2 ion may call an option to exclusively license in ES2B C001, which ExpreS2 ion plans to develop towards human clinical studies. According to the agreement, ExpreS2 ion has the right to call the option to license in AV 001 within 12 months. The option can entail a maximum amount of DKK 1.2M during the full option term. Under the terms of the license agreement, that ExpreS2 ion can opt to execute anytime within 12 months, will contain financial consideration to AdaptVac in the form of an upfront payment at signature of DKK 2.5M (SEK 3.5M), a payment at approval of release of clinical-ready production material of DKK 2.5M (SEK 3.5M) (estimated to be in 2021), a payment for initiation of a clinical Phase I safety trial of DKK 2.5M (SEK 3.5M) (estimated to be in 2022), a payment for initiation of a clinical Phase II efficacy trial of DKK 10M (SEK 14M) (estimated to be in 2023-24) and thereafter aggregated clinical Phase III development and regulatory milestone-based payments of DKK 200M (SEK 285M), and lower single-digit royalty rates of net sales. ExpreS2 ion under the License Agreement plans to develop ES2B C001(HER2-cVLP) until it is clinically validated and ready for partnering. Furthermore, the agreement includes sublicensing rights allowing ExpreS2 ion to partner with a larger biopharmaceutical company on the further commercialisation of ES2B C001, against a fixed percentage of partner payments to be paid by ExpreS2 ion to AdaptVac, in which case remaining financial consideration towards AdaptVac falls away. [1] [2]
Key Development Milestones
In April 2023, ExpreS2ion Biotechnologies presented results from preclinial studies at the 114th Annual Meeting of the American Association for Cancer Research (AACR-2023) [3] .
In May 2022, AdaptVac released pharmacodynamics data from preclinical trial in HER2-positive breast cancer (AdaptVac pipeline; January 2023). In April 2023, results from preclinical study were released by the company [4] .
Financing information
In March 2020, AdaptVac received an Horizon 2020 EU grant of €2.7M as part of the PREVENT-nCoV consortium. The company intends to use the funds for development of the coronavirus vaccine [see Adis Insight Drug Profile800057768] as well as to support production of the needed clinical supply of viral capsid-like particles for clinical projects, including as ES2B C001 [5] .
Patent Information
In January 2020, AdaptVac was granted patent by the USPTO for its “Virus-like particle with efficient epitope display" covering its virus-like particle (VLP) based vaccine treatment for HER2-positive breast cancer. The patent provides intellectual property protection for the U.S. market of AdaptVac’s novel viral capsid-like particle (CLP) technology platform, and any vaccine produced using it [6]
In September 2018, AdaptVac received a notice of allowance in the US for its patent application US 20 180 125 954 A1.The patent is related to the use of VLP-based vaccine for the prophylaxis and/or treatment of a diseases including, but not limited to, cancer, cardiovascular, infectious, chronic, neurological, asthma, immune-inflammatory diseases or disorders. The patent was filed by the University Of Copenhagen with the priority date of January 2015, and once approved, the patent will be valid until January 2025 [7] .
As of September 2018, AdaptVac has pending patent applications for its HER2 breast cancer vaccine in the US and Europe [7] .
In July 2018, the University Of Copenhagen was granted a German patent number DE 16 703 049 T1, entitled "Virus-like particle with efficient epitope display", covering its virus-like particle (VLP) based vaccine, in Germany. The patent is related to a vaccine for use in the prevention and/or treatment of a disease. The vaccine is comprised of a virus capsid protein comprising a first peptide tag, and an antigen which is fused to a second peptide tag, wherein the antigen and the virus capsid protein are connected via an isopeptide bond between the first and the second peptide tag, and wherein both form a virus-like particle, which is the antigen.
The University Of Copenhagen has pending patent applications CA 3 010 975 A1, EP 3 244 915 A1, EP 3 368 068 A1, WO 2016 112 921 A1 and WO 2017 071 713 A1 entitled "Virus like particle with efficient epitope display", covering its virus-like particle (VLP) based vaccine. The patent relates to a technology and method for making a virus-like particle based vaccine with efficient epitope display and capable of inducing a strong and long-term protective immune response. The patent is related to the use of VLP-based vaccine for the prophylaxis and/or treatment of a diseases including, but not limited to, cancer, cardiovascular, infectious, chronic, neurological, asthma, allergy, immune-inflammatory diseases or disorders.
Drug Properties & Chemical Synopsis
- Route of administration Parenteral
- Formulation unspecified
- Class Antineoplastics, Cancer vaccines, Immunotherapies, Virus-like particle vaccines
- Mechanism of Action Immunostimulants
-
WHO ATC code
J07B-X (Other viral vaccines)
L (Antineoplastic and Immunomodulating Agents)
R07 (Other Respiratory System Products)
-
EPhMRA code
J7E9 (All other viral vaccines)
L (Antineoplastic and Immunomodulating Agents)
R7X (All Other Respiratory System Products)
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| ES2B C001 | Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10) | Outcome Measure |
| FSH | Eligibility Criteria | |
| Interleukin-6 (IL-6) | Outcome Measure | |
| Interleukin-8 (IL-8) | Outcome Measure | |
| Monocyte chemoattractant protein-1 (MCP-1/CCL2) | Outcome Measure |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| HER2 positive breast cancer | - | - | Preclinical | USA | Parenteral / unspecified | AdaptVac | 01 Mar 2018 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| AdaptVac | Originator | Denmark |
| AdaptVac | Owner | Denmark |
| ExpreS2ion Biotechnologies | Licensee | Denmark |
| University of Copenhagen | Technology Provider | Denmark |
| ExpreS2ion Biotechnologies | Technology Provider | Denmark |
Scientific Summary
Pharmacodynamics
Summary
In preclinical study, ES2B C001 showed significant tumour growth inhibition ability in HER2-transgenic mice. Mice were injected with HER2-positive tumors followed by vaccination every two weeks one week after challenge. All control mice had lung nodules, whereas all mice vaccinated with ES2B C001 formulated in an adjuvant were metastasis-free. Furthermore, 73% of mice vaccinated with ES2B C001 without adjuvant were metastasis-free and remaining had only 1-2 lung nodules (AdaptVac pipeline; January 2023).
Results from preclinical study showed that ES2B-C001 vaccination inhibited the onset, growth, and metastatic spread of HER-2 positive mammary carcinomas in mice. The vaccine induced strong and persistent antibody responses that inhibited human HER-2+ breast and gastric cancer cells in vitro [4] .
In preclinical studies, untreated mice developed progressive tumours within one month, whereas 70% of mice vaccinated without adjuvant and all mice vaccinated with adjuvant were tumour-free one year after cell challenge. Vaccination of young, tumour-free Delta16 mice completely prevented tumour onset for more than one year. Delta16 mice challenged i.v. with QD HER-2-positive cell line mice developed a mean of 68 lung nodules, whereas 73% of mice therapeutically vaccinated without adjuvant, and all mice vaccinated with E2SB C001+ISA 51, were free from metastases [3] .
Immunogenicity
In preclinical studies, ES2B C001 induced copious anti-HER-2 antibodies of all IgG subclasses, ranging 1-10mg/mL in FVB mice and 0.1-1mg/mL in Delta16 mice. The antibody titers remained very high for 6-10 months after the last vaccination. Antibodies inhibited the 3D growth of human HER-2+++ and HER-2++ breast cancer cells, of trastuzumab resistant cells and of gastric carcinoma cells. Vaccination increased interferon-gamma secreting cells in the spleen, as evaluated by ELISPot (21±3 spots/2x105 cells) [3] .
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 31 Dec 2024 | Trial Update | AdaptVac plans a phase II efficacy trial for Breast cancer in 2023 or 2024 [1] | 28 Feb 2020 |
| 31 Mar 2024 | Trial Update | AdaptVac plans a phase I trial for HER2-positive breast cancer in Q1 2024 (Parenteral) (AdaptVac pipeline; January 2023) [1] | 23 Jan 2023 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 18 Apr 2023 | Scientific Update | Pharmacodynamics data from a preclinical study in Breast cancer released by ExpreS2ion Biotechnologies [4] Updated 21 Apr 2023 |
| 14 Apr 2023 | Scientific Update | Pharmacodynamics and immunogenicity data from preclinical trial in HER2-positive-breast-cancer presented at the 114th Annual Meeting of the American Association for Cancer Research (AACR-2023) [3] Updated 25 May 2023 |
| 23 Jan 2023 | Active Status Review | ES2B C001 is still in preclinical phase for HER2-positive breast cancer in USA (AdaptVac pipeline; January 2023) Updated 23 Jan 2023 |
| 31 May 2022 | Scientific Update | Pharmacodynamics data from a preclinical trial in HER2-positive breast cancer released by AdaptVac (AdaptVac pipeline; January 2023) Updated 23 Jan 2023 |
| 28 Apr 2022 | Phase Change - No development reported | No recent reports of development identified for preclinical development in HER2-positive-breast-cancer in USA (Parenteral) Updated 28 Apr 2022 |
| 17 Nov 2021 | Biomarker Update | Biomarkers information updated Updated 20 Nov 2021 |
| 02 Feb 2021 | Licensing Status | ExpreS2ion Biotechnologies in-licenses ES2B C001 (formerly AV 001) from AdaptVac [2] Updated 05 Feb 2021 |
| 26 Feb 2020 | Trial Update | AdaptVac plans a phase I trial for HER2-positive breast cancer in Q1 2024 (Parenteral) (AdaptVac pipeline; January 2023) [1] Updated 23 Jan 2023 |
| 26 Feb 2020 | Licensing Status | AdaptVac signs an option to license agreement with ExpreS2 ion Biotechnologies to develop AV 001 [1] Updated 28 Feb 2020 |
| 26 Feb 2020 | Trial Update | AdaptVac plans a phase II efficacy trial for Breast cancer in 2023 or 2024 [1] Updated 28 Feb 2020 |
| 08 Jan 2020 | Patent Information | AdaptVac receives patent and has patent protection for Virus-like particle with efficient epitope display platform in USA. [6] Updated 08 Jan 2020 |
| 10 Sep 2018 | Patent Information | AdaptVac has patents pending for its HER2 breast cancer vaccine in USA and Europe [7] Updated 18 Sep 2018 |
| 10 Sep 2018 | Patent Information | AdaptVac receives patent allowance for virus like particle-based vaccine for the treatment of HER2-positive breast cancer in USA [7] Updated 18 Sep 2018 |
| 12 Jul 2018 | Patent Information | AdaptVac and the University Of Copenhagen has patent protection for virus like particle-based vaccine in Germany Updated 18 Sep 2018 |
| 01 Mar 2018 | Phase Change - Preclinical | Preclinical trials in HER2-positive-breast-cancer in USA (Parenteral) Updated 24 Oct 2018 |
| 15 Jan 2015 | Patent Information | AdaptVac and the University Of Copenhagen has patents pending for virus like particle-based vaccine in Canada, Europe and World Updated 18 Sep 2018 |
References
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AdaptVac Signs AV001 Option to License Agreement with ExpreS2 ion.
Media Release -
AdaptVac Signs AV001 License Agreement with ExpreS2ion.
Media Release -
Ruzzi F, Palladini A, Clemmensen S, Strobaek A, Buijs N, Domeyer T, et al. Preclinical activity of ES2B-C001, a human candidate HER-2 virus-like particle (VLP) vaccine, against mammary carcinoma onset and metastasis. AACR-2023 2023; abstr. 687 / 7.
Available from: URL: https://www.abstractsonline.com/pp8/#!/10828/presentation/4010 -
ExpreS2ion announces poster presentation on ES2B-C001 at the AACR Annual Meeting 2023.
Media Release -
AdaptVac's ground-breaking technology central to new EUR2.7M EU grant funded COVID-19 vaccine effort.
Media Release -
Granting of AdaptVac's core platform technology patent in the United States.
Media Release -
ExpreS2ion's joint venture, AdaptVac, receives notice of allowance in the U.S. for its breast cancer vaccine patent.
Media Release
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