Author: Thomas M. Lancaster ; Yannick van Sleen ; Hendrikus H. Boersma ; Gooitzen M. van Dam ; Vidhya Rao ; Thillainaygam Sathiyaseelan ; Sravya Kotha ; Melanie M. Scully ; Schelto Kruijff ; Todd C. Zion ; Ari Aminetzah ; Shashikant Nagre ; Frans Sollie ; Yester F. Janssen ; Debbie van Baarle ; David G. Alleva ; Eline A. Feitsma ; Freedom M. Green ; Sylaja Murikipudi ; Nishit J. Shah ; Shannon E. Ronca ; Andrea R. Delpero ; Maarten Brom ; Ramya Ragupathy ; Jeffrey R. Haworth

BACKGROUND:

Previous interim data from a phase I study of AKS-452, a subunit vaccine comprising an Fc fusion of the respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (SP/RBD) emulsified in the water-in-oil adjuvant, Montanide™ ISA 720, suggested a good safety and immunogenicity profile in healthy adults. This phase I study was completed and two dosing regimens were further evaluated in this phase II study.

METHODS:

This phase II randomized, open-labelled, parallel group study was conducted at a single site in The Netherlands with 52 healthy adults (18 - 72 years) receiving AKS-452 subcutaneously at one 90 µg dose (cohort 1, 26 subjects) or two 45 µg doses 28 days apart (cohort 2, 26 subjects). Serum samples were collected at the first dose (day 0) and at days 28, 56, 90, and 180. Safety and immunogenicity endpoints were assessed, along with induction of IgG isotypes, cross-reactive immunity against viral variants, and IFN-γ T cell responses.

RESULTS:

All AEs were mild/moderate (grades 1 or 2), and no SAEs were attributable to AKS-452. Seroconversion rates reached 100% in both cohorts, although cohort 2 showed greater geometric mean IgG titers that were stable through day 180 and associated with enhanced potencies of SP/RBD-ACE2 binding inhibition and live virus neutralization. AKS-452-induced IgG titers strongly bound mutant SP/RBD from several SARS-CoV-2 variants (including Omicrons) that were predominantly of the favorable IgG1/3 isotype and IFN-γ-producing T cell phenotype.

CONCLUSION:

These favorable safety and immunogenicity profiles of the candidate vaccine as demonstrated in this phase II study are consistent with those of the phase I study (ClinicalTrials.gov: NCT04681092) and suggest that a total of 90 µg received in 2 doses may offer a greater duration of cross-reactive neutralizing titers than when given in a single dose.

01 Feb 2022·VaccineQ3 · MEDICINE

Phase I interim results of a phase I/II study of the IgG-Fc fusion COVID-19 subunit vaccine, AKS-452

Q3 · MEDICINE

Article

Author: Delpero, Andrea R ; van Dam, Gooitzen M ; Lancaster, Thomas M ; Feitsma, Eline A ; Scully, Melanie M ; Shah, Nishit J ; Green, Freedom M ; Nagre, Shashikant ; Sollie, Frans ; Alleva, David G ; Kotha, Sravya ; Boersma, Hendrikus H ; Janssen, Yester F ; Brom, Maarten ; Murikipudi, Sylaja ; Sathiyaseelan, Thillainaygam ; Aminetzah, Ari ; Zion, Todd C ; Ragupathy, Ramya ; Haworth, Jeffrey R ; Kruijff, Schelto ; Rao, Vidhya ; Ronca, Shannon E

To address the coronavirus disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recombinant subunit vaccine, AKS-452, is being developed comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain (SP/RBD) antigen and human IgG1 Fc emulsified in the water-in-oil adjuvant, Montanide™ ISA 720. A single-center, open-label, phase I dose-finding and safety study was conducted with 60 healthy adults (18-65 years) receiving one or two doses 28 days apart of 22.5 µg, 45 µg, or 90 µg of AKS-452 (i.e., six cohorts, N = 10 subjects per cohort). Primary endpoints were safety and reactogenicity and secondary endpoints were immunogenicity assessments. No AEs ≥ 3, no SAEs attributable to AKS-452, and no SARS-CoV-2 viral infections occurred during the study. Seroconversion rates of anti-SARS-CoV-2 SP/RBD IgG titers in the 22.5, 45, and 90 µg cohorts at day 28 were 70%, 90%, and 100%, respectively, which all increased to 100% at day 56 (except 89% for the single-dose 22.5 µg cohort). All IgG titers were Th1-isotype skewed and efficiently bound mutant SP/RBD from several SARS-CoV-2 variants with strong neutralization potencies of live virus infection of cells (including alpha and delta variants). The favorable safety and immunogenicity profiles of this phase I study (ClinicalTrials.gov: NCT04681092) support phase II initiation of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain.

NPJ vaccines

Immunogenicity phase II study evaluating booster capacity of nonadjuvanted AKS-452 SARS-Cov-2 RBD Fc vaccine

Article

Author: Delpero, Andrea R ; van Dam, Gooitzen M ; Lancaster, Thomas M ; Feitsma, Eline A ; Scully, Melanie M ; Shah, Nishit J ; Green, Freedom M ; Alleva, David G ; Nagre, Shashikant ; Boersma, Hendrikus H ; Kotha, Sravya ; Janssen, Yester F ; Shaw, Stephen A ; Brom, Maarten ; Murikipudi, Sylaja ; Sathiyaseelan, Thillainaygam ; Zion, Todd C ; Aminetzah, Ari ; Ragupathy, Ramya ; Haworth, Jeffrey R ; Kruijff, Schelto ; Ronca, Shannon E ; Rao, Vidhya

Abstract:

AKS-452, a subunit vaccine comprising an Fc fusion of the ancestral wild-type (WT) SARS-CoV-2 virus spike protein receptor binding domain (SP/RBD), was evaluated without adjuvant in a single cohort, non-randomized, open-labelled phase II study (NCT05124483) at a single site in The Netherlands for safety and immunogenicity. A single 90 µg subcutaneous booster dose of AKS-452 was administered to 71 adults previously primed with a registered mRNA- or adenovirus-based vaccine and evaluated for 273 days. All AEs were mild and no SAEs were attributable to AKS-452. While all subjects showed pre-existing SP/RBD binding and ACE2-inhibitory IgG titers, 60–68% responded to AKS-452 via ≥2-fold increase from days 28 to 90 and progressively decreased back to baseline by day 180 (days 28 and 90 mean fold-increases, 14.7 ± 6.3 and 8.0 ± 2.2). Similar response kinetics against RBD mutant proteins (including omicrons) were observed but with slightly reduced titers relative to WT. There was an expected strong inverse correlation between day-0 titers and the fold-increase in titers at day 28. AKS-452 enhanced neutralization potency against live virus, consistent with IgG titers. Nucleocapsid protein (Np) titers suggested infection occurred in 66% (46 of 70) of subjects, in which only 20 reported mild symptomatic COVID-19. These favorable safety and immunogenicity profiles support booster evaluation in a planned phase III universal booster study of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain.

News (Medical) associated with AmbiVax-C

26 Feb 2024

·www.businesswire.com

Akston Biosciences' AKS-452 Vaccine Study Published in Nature, Showcasing Ambifect® Platform's Versatility

BEVERLY, Mass.--( BUSINESS WIRE )-- Akston Biosciences , dedicated to accelerating the next revolution in Animal Health, announced the publication in Nature Vaccines of phase II study results for AKS-452, based on Akston’s Ambifect® Fc-fusion protein platform . This Netherlands study showed the ability of a 90 ug subcutaneous dose to safely boost the immune response of individuals previously primed with a registered mRNA- or adenovirus-based SARS-CoV-2 vaccine. Fc-fusion protein vaccines derived from Akston’s platform provide a unique set of benefits, including inherent stability at ambient temperatures and low-cost, high-volume manufacture. AKS-452 is a subunit vaccine consisting of an Fc fusion of the SARS-CoV-2 spike protein receptor binding domain (SP/RBD). While all phase II study subjects showed pre-existing SP/RBD binding and ACE2-inhibitory IgG titers, 60–68% responded to AKS-452 via ≥2-fold increase from days 28 to 90. Similar response kinetics against RBD mutant proteins (including omicrons) were observed but with slightly reduced titers relative to the wild type. Earlier studies in Europe and India showed the utility of AKS-452 as a primary vaccine, and it has received approval for use in registration studies in India to test boosting and broadening immunity. Taken together, the clinical results have demonstrated that a vaccine built on the Ambifect® platform could be a safe, effective, and practical way to achieve large-scale primary and booster vaccination. “Akston has also made significant strides in demonstrating the Ambifect® platform's potential beyond infectious disease vaccination,” said Todd Zion, Ph.D., President & CEO of Akston Biosciences. “We have also demonstrated that it can be applied to therapeutic vaccination, whereby the immune system is recruited to target proteins involved in non-communicable diseases such as dementia, chronic pain, and cancer.” To further apply the Ambifect® platform, Akston recently spun out all human clinical vaccine applications with lead candidates targeting misfolded proteins involved in neurodegenerative diseases including Alzheimer’s and infectious diseases including Middle East Respiratory Syndrome (MERS) and Dengue fever. “Akston’s primary focus remains on animal health, where we are currently advancing lead therapeutic vaccines against nerve growth factor for chronic pain and IL-31 for atopic dermatitis," said Dr. Zion. About Akston Biosciences Akston Biosciences Corporation is dedicated to accelerating the next revolution in Animal Health by inventing, developing, and manufacturing breakthrough protein therapeutics for veterinary use. Its vertically integrated capabilities, including a kilogram-scale cGMP manufacturing facility dedicated to Animal Health, can significantly reduce the time and cost from discovery to commercial introduction. Akston leverages its Ambifect® Fc-fusion protein platform to create innovative, extended-duration biologics and therapeutic vaccines. Its facilities are located in Beverly, Mass. Additional information is available at akstonbio.com .

VaccineClinical ResultPhase 2mRNAPhase 1

17 Aug 2023

·www.biospace.com

Akston Biosciences to Focus on Strong Animal Health Pipeline

BEVERLY, Mass.--(BUSINESS WIRE)-- Akston Biosciences Corporation announced today that it will focus on inventing, developing, and manufacturing breakthrough protein therapeutics for Companion Animal Health, utilizing its versatile Ambifect™ Fc-fusion platform and its Beverly, Massachusetts cGMP biologics manufacturing facility. Akston is spinning off its infectious disease vaccine and human Type 1 Diabetes prevention lines of business into two wholly-owned subsidiaries: Vakston, Inc. and Diamune Therapeutics, Inc. Akston’s most advanced Animal Health candidates, AKS-321d and AKS-425c, are once-a-week insulins designed to treat canine and feline diabetes. Both are licensed to and are being developed in partnership with Dechra Pharmaceuticals, Plc, a global veterinary pharmaceuticals company. Based on responses from the owners of animals treated to date, Akston believes that upon regulatory clearance both can achieve rapid market adoption and are potential Animal Health “blockbusters.” The company’s pipeline also includes AKS-544d, which targets chronic pain in canines, and AKS-197d, an insulin receptor down-regulator for treating canine cancers. “As with human health 20 years ago, protein therapeutics are now poised to revolutionize companion Animal Health,” said Todd Zion, Ph.D., President & CEO of Akston Biosciences. “Our goal is to be a major player in this revolution, through focused efforts that leverage our ability to develop products from concept through commercial manufacturing.” In addition to inventing and developing its own therapeutic candidates, Akston serves as a Contract Development and Manufacturing Organization (CDMO) for Animal Health companies, using its vertically integrated capabilities, including: Multi-kilogram-scale cGMP biologics clean-room factory Product-scale Process Development and Quality Control facilities Pharmacology laboratory “Spinning out Vakston and Diamune allows each new company to continue developing its promising candidates at the proper pace, reflecting their own investment thesis,” said Rahul Bhansali, Managing Partner at Formation Venture Engineering, an Akston shareholder that is focused on game-changing life science technologies. “We are taking a leading role with Vakston to continue moving the AKS-452 vaccine forward and expanding beyond COVID-19 to apply Akston’s Ambifect™ Fc-fusion platform to a range of infectious diseases.” About Akston Biosciences Akston Biosciences Corporation invents, develops, and manufactures breakthrough protein therapeutics for Companion Animal Health. It was founded by the team that developed the world’s first clinical glucose-responsive insulin at SmartCells, Inc. (sold to Merck & Co.). Akston uses its Ambifect™ Fc-fusion platform to design its own novel candidates and operates a multi-kilogram-scale cGMP biologics clean-room factory dedicated to Animal Health therapeutic production. The company also provides Contract Development and Manufacturing Organization (CDMO) services for other Animal Health companies. Additional information is available at .

VaccinemRNA

08 Mar 2023

·www.businesswire.com

Akston Biosciences Ends Vaccine Partnership with Stelis, Continues to Advance COVID Universal Booster EUA

BEVERLY, Mass. and BANGALORE, India--( BUSINESS WIRE )--Akston Biosciences Corporation, a developer of new classes of biologic therapeutics, announced today it has ended its AKS-452 licensing, manufacturing, and commercialization agreement with Stelis Biopharma Limited, an arm of Strides Pharma Science Ltd. Akston has reclaimed all rights to AKS-452, a room temperature stable, low-cost, protein subunit COVID-19 vaccine. AKS-452 has completed a Phase II/III clinical trial in India, with data showing robust safety profile and a 91% seroconversion rate at Day 56. Volunteers in the study had antibody titers that persisted at statistically-significant high levels through six months, with serum showing protection against variants of concern, including Delta and Omicron. Akston is now working with a new CDMO in India to produce the promising AKS-452 COVID "universal" booster vaccine. The results of a Phase I/II randomized, open-labelled study in The Netherlands and published in Vaccine showed that seroconversion rates reached 100% with enhanced potencies of SP/RBD-ACE2 binding inhibition and live virus neutralization. In a Phase II study in the Netherlands of AKS-452 as a “universal” booster vaccine, 93% of subjects previously vaccinated with Pfizer, Moderna, Johnson & Johnson (Janssen), and AstraZeneca vaccines showed an increase in neutralizing antibody titers after receiving a single dose. The average neutralization titers across all subjects increased 4-fold against the Wuhan strain and 5-fold against the Omicron variants at Day 28. There were no safety issues reported. Todd Zion, Ph.D., President & CEO of Akston Biosciences , said, “I am confident that AKS-452 can attain Emergency Use Authorization (EUA) in India, especially as a ‘universal’ booster vaccine capable of increasing and broadening people’s immune response as their previous immunity wanes and new variants arise. We concluded that Akston and a different CDMO were better placed to move ahead the AKS-452 development plan at a rapid pace, so we reclaimed the rights.” About Akston Biosciences Akston Biosciences Corporation leverages its Ambifect™ Fc-fusion protein platform to develop and manufacture new classes of biologics, including vaccines, ultra-long-acting insulins, and autoimmune disease therapies. Founded by the team that developed the world’s first clinical glucose-responsive insulin at SmartCells, Inc. (sold to Merck & Co.), Akston owns and operates a cGMP biologics cleanroom facility that manufactures kilogram-scale batches of drug substance. This, along with its research and process development laboratories, are located at its Beverly, Mass. location. Additional information is available at www.akstonbio.com .

VaccineClinical ResultLicense out/inPhase 2mRNA

100 Deals associated with AmbiVax-C

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Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Phase 3	India	Tenshi Healthcare Pte Limited	21 Mar 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Corporate Publications Manual	Phase 2/3	COVID-19	1,600	AKS-452	yenlpkexzu(zicnxsabxi) = no significant safety issues jelpeypvqu (gndqekqnkl )	Positive	24 Jun 2022

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