Sedan ExpreS2ion Biotechnologies inledde utvecklingen av ett vaccin mot Covid-19 har bolaget rusat på börsen. För att accelerera tillväxten ytterligare har man nu inlett en kapitalrunda som totalt kan tillföra upp till 216 Mkr, fördelat på en emission om 131 Mkr och två serier teckningsoptioner om totalt maximalt 85 Mkr. BioStock har talat med nya vd Bent U Frandsen om framtidsutsikterna, kapitalanskaffningen och jakten på nya vacciner.

ExpreS2ion Biotechnologies grundades 2010 och var då ett tjänstebolag, men sedan Bent U Frandsen tillträdde vd-posten i december 2019 har man utökat sin verksamhet till att även inkludera en egen projektpipeline.

Patenterad teknikplattform ExpreS2 

Bolaget affärsmodell bygger på att utveckla, producera och leverera terapeutiska eller diagnostiska proteiner, samt att på kort sikt generera intäkter genom att licensiera ut bolagets patenterade teknikplattform – ExpreS2 – till forskningsinstitut och globala återförsäljare.

ExpreS2-plattformen är framtagen för att effektivisera icke-klinisk utveckling och produktion av komplexa proteiner för nya vacciner och ny diagnostik. Idag har bolaget en bred kund- och samarbetsbas som sträcker sig världen över. Deras nätverk omfattar över 100 kunder och partnerskap som etablerats sedan starten 2010, bland andra läkemedelsjättarna Roche, Novartis och Janssen (J&J) samt välkända forskningsorganisationer som University of Copenhagen, University of Oxford och Harvard Medical School.

Numera kombinerar ExpreS2ion alltså denna framgångsrika tjänsteverksamhet med att utveckla en intern pipeline av biofarmaceutiska läkemedels- och vaccinkandidater för att maximera aktieägaravkastningen. För denna verksamhetsdel är målet är att bedriva preklinisk och tidig klinisk utveckling i egen regi för att sedan ingå licensavtal eller partnerskap med större aktörer. Den övergripande vision är att bli en ledande aktör inom immunterapi och infektionssjukdomar.

Vidare har ExpreS2ion genom sitt delägda joint venture-bolag, AdaptVac – som bildades 2017 – tillgång till en unik kapsidvirusliknande partikel (cVLP)-teknologi, en innovativ metod för att framställa effektiva vacciner.

Kampen mot corona

I februari inledde ExpreS2ion en uppmärksammad satsning på att ta fram ett vaccin mot Covid-19. I samband med den nya satsningen startades även ett paneuropeiskt konsortium, PREVENT-nCoV, som bland andra inkluderar AdaptVac, för att samla befintlig expertis och tillsammans ta fram ett kraftfullt vaccin mot Covid-19.

Projektet har redan genererat data som visar en mycket hög grad av virusneutralisering i djurmodeller. Därutöver har vaccinprojektet lyckats tecknat ett Good Manufacturing Practice (GMP)-certifierat avtal med AGC Biologics för produktion av vaccinet samt ingått ett globalt licensavtal med Bavarian Nordic avseende sena kliniska studier, marknadsföring och distribution.

Vaccinkandidaten beräknas inleda en klinisk fas I/IIa-studie innan årsskiftet och interim resultat väntas kunna presenteras i slutet av första kvartalet 2021.

Partnerskap för vaccin mot bröstcancer

I februari ingick ExpreS2ion även ett optionsavtal med AdaptVac för att licensiera AV001, en vaccinkandidat som utvecklas mot bröstcancer. Avtalet ger ExpreS2ion alternativet att ingå ett exklusivt globalt licensavtal för AV001-programmet, och optionen är giltigt till februari 2021. I augusti meddelade ExpreS2ion sina intentioner att nyttja optionen.

AV001 har sedan tidigare visat prov på bra immunitetsrespons och anti-tumöreffekter i djurmodeller och den första studien i människa förväntas inledas i början av 2022.

Övriga satsningar på virusvaccin 

ExpreS2ion är även involverade i ett antal program för malariavaccin, varav två är under klinisk utveckling. Det längst avancerade projektet är ett RH5.1-malariavaccin som visat positiva data i en fas I/IIa-studie och resultat från en fas IIa-studie väntas innan årsslutet 2020. Dessutom planerar bolaget att inleda ytterligare en fas Ia-studie för en annan vaccinkandidat i en malariadrabbad region i Afrika.

Bolaget deltar dessutom i utvecklingen av nästa generations influensavaccin. Här bidrar ExpreS2ion med sin ExpreS2-plattform i ett offentligt finansierat konsortium som består av offentliga och privata FoU-organisationer i EU, USA och Indien. Målet är att ta en eller flera vaccinkandidater till kliniska prövningar i fas I/IIa i Europa och Indien.

Kapitalanskaffning i ljuset av nytt bolagsfokus

För att finansiera sin breda, och växande, pipeline är nästa steg för bolaget att nu stärka kassan genom en företrädesemission som kan tillföra bolaget upp till 131 Mkr. Teckningsperioden löper mellan 5 och 19 oktober.

Emissionen kommer med två vidhängda serier teckningsoptioner, TO4 med teckningstid i april 2021 och TO5 med teckningstid i augusti/september 2021, som tillsammans kan tillföra ytterligare maximalt 85 Mkr.

VD kommenterar

Bent U. Frandsen, vd ExpreS2ions Biotechnologies.

BioStock kontaktade vd Bent U Frandsen för att få veta mer om bolagets vaccinationsteknologi, den nya strategin han initierat och den pågående kapitalrundan.

Mr. Bent U Frandsen, you were appointed the new CEO in December 2019. Can you please briefly describe your professional background and how you landed this position at ExpreS2ion? 

– I have a Master of Science degree in Finance and Strategic Planning from Copenhagen Business School from 1993 and have a solid track record from the Life Sciences industry since joining the pharmaceutical company H. Lundbeck A/S in 1997. I have always worked closely with world-class Research & Development scientists in roles, where I have focused on licensing, business development and commercial affairs.

– I started at ExpreS2ion Biotechnologies in March 2016 and was at that time responsible for sales and marketing, including playing an instrumental role in the public listing of ExpreS2 Since the IPO in 2016, we have succeeded in increasing the revenues by an average annual growth rate of more than 35%. In December 2019 the Board of Directors appointed me CEO to focus the company on value-creating pipeline activities.

Earlier this year, the company announced a strategic shift from being a service company to a pipeline company. Can you explain the reason for the new strategy and how it will affect the company’s business?

– Despite the increase in revenues from the service business, it has so far not been a profitable business, although we have been on a growth trajectory towards positive net results. Even with a profit from the service business, the real value in the company lies in exploiting our unique technologies to develop own vaccine products.

– With our advantageous protein production system ExpreS2, and thanks to the semi-owned joint venture AdaptVac, we can make very effective vaccines, and so, the strategy is to seek early development programmes that we can take into clinical validation and create value through strong license and development collaborations.

To expand on your technology platform, could you give a short explanation of how the technology works and what the major medical benefits of your platform are?

– First of all, ExpreS2 is a patented protein production system based on an improved expression of proteins made in Drosophila S2 insect cells. Drosophila cells come from fruitfly embryos and were first discovered by Schneider in the 70’es. The S2 in our company name ExpreS2ion is due to these special insect cell lines. ExpreS2ion’s founders discovered that these insect cells could be improved to very quickly generate high quality proteins and high yields, and furthermore making proteins that normally were difficult to express in common systems. The ExpreS2 system has proven to be the only production system able to make certain protein antigens, that are applied in malaria vaccine research, and is now used in clinical-stage malaria studies.

– Secondly, it is important to understand, that it is awesome to possess the ExpreS2 technology to make the active ingredient in a given vaccine, but it is also important to have access to AdaptVac’s cVLP technology, which can make a vaccine very effective, meaning making an immune response that is faster, stronger, and longer. The cVLP technology, which was invented by Ali Salanti’s research group at the Center of Medical Parasitoloy at the University of Copenhagen, consists of a molecule with a structure which is non-viral and completely safe, to which surface we can bind any protein of interest by a unique superglue method. The cVLP technology has now been validated preclinically in animal Proof-of-Concept studies in both Covid-19 and breast cancer vaccine programs.

The company is currently working swiftly to develop a cVLP based Covid-19 vaccine. How is the development proceeding? 

– The cVLP Covid-19 vaccine combines the ExpreS2 technology that makes synthetic non-viral versions of the spike proteins from the virus, and the cVLP technology to bind these spike proteins on a virus-like particle. In our laboratories, we are able to make the non-viral spike proteins and VLPs, respectively, and we have shown that we can mix these to make high density protein display on the surface on VLPs, and that we can use these to vaccinate mice.

– After vaccination, the mice have shown an outstanding ability to generate neutralizing antibodies. Therefore, we hope the vaccine has the potential to be a one-injection-only vaccine when used in man.

– We are now proceeding with various preclinical studies to investigate toxicology, while also working to scale up the manufacturing processes. All is still on the planned development path towards starting the first clinical study in humans before the end of 2020.

ExpreS2ions pipeline. Bildkälla: expres2ionbio.com. Klicka för större bild.

If all works out according to plan, when do you expect to launch the Covid-19 vaccine?

– If all goes according to plan – and this includes that our partner Bavarian Nordic obtains the public funding support necessary to conduct the large-scale phase III study with 10’s of thousands of trial participants required to prove the efficacy and not least safety of the vaccine – it could be on its way to the market already by the end of 2021.

What does the deal with Bavarian Nordic stipulate in terms of future development costs and revenue sharing for the Covid-19 vaccine?

– Through the EU Horizon 2020 grant, we have funding that covers the first clinical phase I/IIa trial. Bavarian Nordic has the responsibility for the clinical development beyond this initial study as well as the marketing and commercial distribution of the Covid-19 vaccine, and this also includes bearing the full costs for these activities.

– The final licensing deal that was announced July 22, 2020, is between AdaptVac and Bavarian Nordic. Under the terms of the agreement, Bavarian Nordic made an upfront payment of EUR 4 million to AdaptVac, in addition to potential future development as well as sales milestones and single to double-digit percentage-tiered royalties. The total deal value, excluding royalties, is up to EUR 136 million, corresponding to SEK 1.4 billion.

– For application of its proprietary protein production system ExpreS2, ExpreS2ion will retain up to EUR 2 million, corresponding to SEK 21 million, of the commercial milestone payments, which are estimated to be recognised as ExpreS2ion revenues during 2021 and 2022 in accordance with the current development plans, as well a double-digit percentage of AdaptVac’s royalty revenue stream.

There is, of course, a global race with many companies working to launch a corona vaccine. Some have already started clinical trials. What makes you believe your project will be successful? 

– Let me start by saying that ExpreS2ion is not in this Covid-19 vaccine field for being first. Together with AdaptVac, we know we will not be the first vaccine available of the more than 160 corona vaccine projects that are going on. However, we have reason to believe we will be the best. The preclinical data we have seen in our project, when comparing with other published preclinical data, are many-fold better on all efficacy parameters, which is very encouraging and promising.

ExpreS2ion is active in several spaces and have recently exercised an option to take over the rights for AV001, a therapeutic breast cancer vaccine. Could you give us a status update on this project?

– Yes, absolutely. Initially let me clarify that we announced on August 18, 2020, that we wish to exercise the exclusive option to in-license AV001. That wish correlates with the current cash raising process, which will provide the funding to proceed with exercising the option and gain full control over this valuable cancer vaccine project.

– When the option to in-license AV001 is exercised, ExpreS2ion will transfer 16 percent of our joint venture ownership in AdaptVac to joint venture partner NextGen Vaccines, following which ExpreS2ion will hold 34 percent and NextGen Vaccines – a spin-out research group out of University of Copenhagen – will hold 66 percent of AdaptVac.

– With that said, AV001 has demonstrated animal Proof-of-Concept in highly relevant transgenic mouse models whereby we have seen, similarly to the Covid-19 project, very promising preclinical effect of this cVLP breast cancer vaccine. The project will now move into a phase of GMP manufacturing preparation, which is expected to take most of 2021, before we can embark on the first clinical study which we aim to initiate during the first half of 2022.

Based on existing evidence, what kind of protection against breast cancer does AV001 have the potential to offer and how will it be positioned on the market?

– The AV001-vaccine targets a human protein called HER2, that cause HER2-positive breast cancer. The ability of AV001 to protect against HER2-induced breast cancer has demonstrated animal Proof-of-Concept and looks highly promising in preclinical models.

– Today, the market is dominated by monoclonal antibody-based therapeutic treatments against HER2-positive breast cancer. With a vaccine, we can make a very effective preventive treatment, and we can also reach the more than 30% of patients who do not respond to the existing therapeutics.

– Furthermore, most people have probably heard of the HPV vaccines, which are currently marketed as preventive treatments against cervical cancer. Actually, these take another VLP approach, and the active ingredient in one of these, CERVARIX from GSK, is even made in other insect cells. Both the ExpreS2 technology and the cVLP technology have highly competitive advantages compared with existing technologies, including manufacturing productivity, efficacy, and safety.

As of now, ExpreS2ion focus on vaccines for Covid-19, breast cancer, malaria and influenza. Could you briefly describe the market potential they are addressing?

– There is a huge unmet need in all of these disease areas that demand safe and effective vaccines. Bear in mind these diseases take the lives of millions of people all over the world every year.

– For Covid-19, I find it quite difficult to assess the market potential, given the global proportions of this pandemic disease. One thing is for sure; I am certain that Bavarian Nordic has the right company profile to commercialize our Covid-19 vaccine on a global scale.

– For breast cancer, as I mentioned before, the market is dominated by monoclonal antibody-based therapeutic treatments, including Herceptin and Perjeta, which are both blockbuster drugs. It is estimated that the breast cancer therapeutics market value is exceeding 10 billion EUR per year, and growing more than 10% per year. I believe that AV001 has a product profile for a vaccine that can gain a significant foothold in this market.

– As for influenza, our research efforts go into developing a universal vaccine that can prevent multiple strains from spreading the flu viruses. The market potential here is estimated in the “more than 5 billion EUR”-range. Ironically, this disease is what was thought to become a pandemic before the corona virus came out of control. I think it is very worthwhile to continue focusing on highly effective influenza vaccines beyond what is available today.

– Finally, malaria is sadly a disease that kills half a million infants and children every year, primarily in poorer regions of the World. We assess that the vaccines within malaria can be made at a cost-friendly level allowing for distribution even here. A research report from Boston Consulting Group has assessed the malaria vaccines market value at around 0.4 billion EUR per year.

Given that you have your own technology platform, do you see any other products or new collaborations further down the line? If so, how are you working to capitalize on these opportunities?

– I am very pleased with the research and development activities that have led to focusing on the current pipeline. We have tremendous experience in addressing multiple other disease areas in the infectious diseases and immunology field.

– A portion of the proceeds from the on-going cash raising process is going towards exploring co-development opportunities and/or technology asset acquisitions in support of our current pipeline and further research and development activities in ExpreS2ion and AdaptVac. This includes exploring whether additional cancer vaccines and/or immunotherapy drugs aimed at chronic diseases, such as allergy, for which there are promising early results, should be advanced into preclinical development.

The company is currently raising 131 MSEK, what are your plans for this capital injection?

– More than half of the capital injection is aimed at exercising the option to in-license the HER2 breast cancer vaccine AV001 from AdaptVac and advance it into human trials in 2022.

– As I just eluded to, about one quarter of the capital injection is going to strengthen ExpreS2ion’s capabilities, pipeline and technology platform, which is an important step in capitalizing on other opportunities at hand.

– About one tenth of the capital injection is dedicated to advancing our efforts in the influenza field. Finally, low portions of the capital injection are planned to support the Covid-19 vaccine project to advance into human trials, as well as to advance certain malaria vaccines in preclinical and clinical development.

The rights issue also comes with two sets of warrants that both have subscription periods during 2021. What was the reasoning behind this setup, and how do you plan to allocate the capital gained from the warrants?

– This financial set-up allows for shareholders to take part in the upside of ExpreS2ion in the near future. This set-up is actually quite unique in Sweden, and I have not experienced this before in Denmark. It’s a great way to participate in further financing, which has an inherent capital benefit built in for investors since the warrant may be exercised with a 30% discount of the average share price at the time of exercise. The capital gained from these warrants will be allocated much to the same proportions as described in my reply to the previous question.

Finally, looking ahead, what is your vision as CEO for ExpreS2ion? What potential do you see for the company in the coming years?

– We are scientific experts in making proteins that can be used in vaccines, as well as therapeutics, diagnostics, and research tools, and now we are even developing our own one-of-a-kind vaccines that have the potential to effectively prevent diseases that claim millions of lives every year. This goes hand in hand with my vision of ExpreS2ion Biotech becoming a global market leader within infectious diseases and immunology.

– Needless to say, I know there is also more risk in following a pipeline strategy instead of a service business strategy, but on the other hand the potential rewards are also so much larger.

– Our company tag line is “Proteins For Life”, and that is exactly what we excel in and pursue. I see a great future for the company, and I will not be surprised if we in the coming years have license income from a vaccine product on the market, and have a world-class pipeline with even more clinical-stage and partner-attractive assets. It is difficult not to be very enthusiastic and very positive on the outlook, and I thank my employees and collaborators every day for being in a position to steer ExpreS2ion towards an even higher valued business.

 

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