Az akadémiai-ipari együttműködések szerepe a gyógyszerfejlesztésben pandémia idején
Authors: Keserű György Miklós 
Published: October 2021

Összefoglaló. Egészen az ezredfordulóig a gyógyszeripari
kutatás-fejlesztés világszerte hagyományosan nagyvállalati keretek között folyt.
Az elmúlt évtizedekben azonban ebben a szegmensben jelentős átrendeződések
tapasztalhatók, ugyanis a korai kutatási és fejlesztési projektek sok esetben
már az egyetemi-akadémiai, illetve kkv-szektorból indulnak. A szervezeti keretek
mellett a fejlesztések szakmai tartalma is változott, a hagyományos kismolekulás
gyógyszerek mellett egyre meghatározóbb szerep jut a biológiai terápiáknak,
valamint a hatóanyagok fejlesztése mára összekapcsolódott a releváns
diagnosztikumok fejlesztésével. A projektek finanszírozásában is fontos
változások történtek, egyre jelentősebb szerep jut az állami KFI
finanszírozásnak és a (kockázati) tőkebefektetéseknek. A gyógyszeripari K+F
szakmai, szervezeti és finanszírozási kereteinek változása jelentősen
felértékelte és szélesítette a korábban is meglévő akadémiai-ipari
kapcsolatokat. Az együttműködések fontos szerepet játszanak a COVID–19 járványra
adott válaszokban is, amit a magyar egyetemek, kutatóintézetek, kis- és
középvállalatok, valamint gyógyszeripari nagyvállalatok részvételével indult
kutatások igazolnak.

Summary. Until the turn of the millennium, pharmaceutical research
and development worldwide had traditionally taken place in pharmaceutical
companies. In recent decades, however, significant rearrangements have been
witnessed, as early-stage research and development projects often start at the
universities or the academic and SME sectors. In addition to the organizational
framework, the professional content has also changed: in addition to traditional
small molecule drugs, biological therapies are playing an increasingly important
role, and the development of active ingredients is now linked to the development
of relevant diagnostics. Important changes have also taken place in the
financing of projects, with public RDI financing and (venture) capital
investments playing an increasing role. Changes in the professional,
organizational and funding frameworks for pharmaceutical R&D have
significantly enhanced and broadened existing academic-industrial relations.
Collaborations also play an important role in the responses to the COVID-19
epidemic, as evidenced by research involving Hungarian universities, research
institutes, small and medium-sized enterprises, and large pharmaceutical
companies. The first example is a collaboration of an academic research group
and a spin-off company formed from this environment. Researchers of the Eötvös
University (ELTE) and others working at the Research Centre for Natural Sciences
(RCNS) applied phage display technology to discover new protease inhibitors.
They established EvolVeritas Ltd, a spin-off company developing high affinity
and high specificity inhibitors of the TMPRSS2 protease that is involved in the
SARS-CoV-2 viral entry to host cells. In a parallel research program, the same
consortium is working on new inhibitors of the MASP2 protease contributing to
the coronavirus mediated activation of innate immunity, particularly the
complement system. This latter approach would result in the effective control of
microthrombosis events associated with serious COVID-19 infections. Both of the
approaches are in the early preclinical phase and further investment would be
needed to push these projects into clinical testing. The second example is a
collaboration between an academic research group and an SME to reposition of
azelastine, an approved antihistamine drug that was found to be effective in
blocking SARS-CoV-2 mediated pathogenesis. After successful preclinical studies,
the partners have now initiated clinical trials to demonstrate the efficacy of
azelastine nasal drops in the prevention and treatment of COVID-19 infections.
The third example is a collaboration of academic research groups, a SME and a
pharmaceutical company. This consortium develops an antibody-like fusion protein
therapeutics that can neutralize the SARS-CoV-2 virus. One component of the
ACE2-Fc fusion protein is the relevant portion of angiotensin-converting enzyme
2 (ACE2) produced by recombinant technologies, which binds to the spike protein
of the pathogen. The virus thus binds to the fusion protein instead of the ACE2
receptors in human cells. Another component is responsible for the long
half-life of IgG, the so-called Fc region. The consortium confirmed that the
ACE2-Fc fusion protein inhibits SARS-CoV-2 infection in cell culture, and
prevents disease in experimental animals. Preclinical development and the
preparation of the core documentation is ongoing, which will soon be submitted
to the European Medicines Agency (EMA) to initiate clinical trials. The final
example is a joint development project that involved a research group, an SME
and two pharmaceutical companies. The objective of this program is process
development and pharmaceutical formulation of favipiravir, a broad-spectrum
antiviral with a treatment potential against COVID-19. The consortium completed
the process development of the active pharmaceutical ingredient (API) and
developed finished dosage formulations available for clinical testing. Clinical
trials are ongoing that aim investigating safety and efficacy of favipiravir in
COVID-19 infected patients. All of the examples described here demonstrate the
power of collaborations that helped the participants to give diverse and
effective responses to the unprecedented pandemic challenge of COVID-19. We
believe that these experiences would encourage the members of the academic and
industry community to formulate further collaborations to tackle the unmet
medical need in our societies.