NEWS

2022 August 16
VRG announces major milestone in chlorotoxin targeted CAR T therapy in glioblastoma

Vascular Research Group announced preclinical results of their proprietary CAR T CTXA8 superior to current clinical stage competitor containing natural CTX

Vascular Research Group (VRG), a peptide-based pharmaceuticals, cellular & gene therapy (CGT) company announced that their proprietary chlorotoxin (CTX) analogue, CTXA8, an antigen recognition domain in CAR T-cells, shows high potency in eliminating glioblastoma multiforme (GBM) cells in a preclinical in vitro GBM model. CTXA8 CAR modified T-cells demonstrated superior efficacy over the CAR T candidate employing natural CTX currently in a Phase 1 clinical trial. CTXA8 has been developed using VRG’s "designer miniprotein" platform. "We are very excited about these preclinical results that are in line with CTXA8’s superior affinity and selectivity towards MMP2 versus the natural CTX containing clinical stage competitor" - said Dr. Zalán Péterfi, Managing Director of VRG. "We look forward to reaching out and working with prospective partners to translate these promising developments into significant improvements in patient outcomes".

About CAR-T therapy targeting brain tumors: CAR T-cells are modified white blood cells expressing a chimeric antigen receptor (CAR) against a specific tumor antigen that holds the potential of identification and elimination of cancer cells. High overexpression of MMP2 protein in GBM has recently been utilized as a new target and the initial results from the ongoing Phase 1 trial show that CTX targeted CAR T therapy could be a game changer for this indication. The safety and efficacy of CAR T therapies strongly depend on the specificity and selectivity of the tumor-targeting domain of the chimeric antigen receptor. Using its designer "miniprotein" platform, VRG has developed a proprietary CTX analog, CTXA8 that provides a solution for directed antitumor activity. CTXA8 as a targeting agent of CAR T-cells, exerts a major effect on MMP2-overexpressing GBM while sparing normal tissues with low MMP2 expression. VRG’s latest results show that CTXA8 CAR T-cells demonstrate faster and improved killing of tumor cells within 24 hours with an effector-target ratio of 1:3, which predicts higher efficacy and lower off-tumor effect compared to the CAR T therapy with original CTX currently in Phase 1. The increased efficacy of CTXA8-based CAR T therapy is due to the increased affinity and selectivity of CTXA8 versus original CTX towards MMP2 overexpressing tumor cells. This is further supported by a cytokine release assay in which CTXA8 CAR T-cells secreted 3 times more IFN gamma than CTX CAR Ts.

About VRG’s miniprotein platform: The "designer miniprotein" technology platform, based on naturally occurring toxins and other peptide molecules, employs a directed evolution approach for selecting the best candidates from a peptide mega-library with more than a million randomly generated variants.

About VRG: Vascular Research Group is a biopharmaceutical company located in Budapest, Hungary. VRG is a part of the Vascular Group with various business activities in the healthcare industry. VRG generates proprietary proteins/peptides using a directed evolutionary approach and employs them as small protein pharmaceuticals or as Cellular & Gene Therapeutics. VRG’s strategy is to cure diseases via targets and MoAs that cannot be reached with traditional approaches using small molecules or natural peptide-based pharmaceuticals.

2022 May 2
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New member to the team
We are happy to announce that Anna Hollósi, MSc, has joined our team as a scientist on 2 May 2022. Anna completed her MSc in Biochemical Engineering specialized in Applied Biotechnology at the Budapest University of Technology and Economics. As a student researcher she gained experience in Pathology and Pathobiochemistry at the Second Department of Pathology of Semmelweis University. Her main area of research was the study of breast tumors and the associated signalling pathways. Anna will be completing her PhD at the Department of Biophysics and Radiation Biology of Semmelweis University. During her PhD she focused on understanding the mechanism of metastasis and mapping the underlying signalling pathways.

2022 February 1
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New member to the team
We are pleased to announce that Anna Hajdara, MSc, has joined our team as a scientist on 1 February 2022. Anna is a medical biotechnologist and soon will be completing her PhD at the Stem Cell Laboratory of the Semmelweis University, Department of Dermatology, Venerology and Dermatooncology. Her main research field was the effect of neural and immunological factors on skin stem cells, hence her arrival will add a valuable knowledge to VRG’s projects. During her university years she had also gained experience in bioengineering and neurodegenerative disease research.

2022 January 31
We have launched our cutting-edge DREADD project (Designer Receptor Exclusively Activated by Designer Drug).
DREADDs are exclusively activated by their pharmaceutical ligand, the so-called actuator. CNS-delivered artificial DREADDs have no physiological effects without their actuator, offering a flexible and adaptive control of the timing and intensity of the effect. This technique can be employed to develop a safe, adjustable alternative of current neurosurgery techniques, such as deep brain stimulation and local lesion. Moreover, molecular targeting solutions (e.g. promoters) allows disctinction between neuronal populations not only based on their localization, but also based on their neurochemical attributes. On the long run, non-surgical delivery may provide additional benefits to this platform.

2022 January 3
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New member to the team
We are happy to announce that József Murányi, PhD has joined our team as scientist on 3 January 2022. József completed his MSc in chemical engineering specialized in medicinal chemistry at the Budapest University of Technology and Economics. He received his PhD degree in Pharmaceutical Sciences at Semmelweis University, Budapest. József is an expert in preparative organic chemistry specialized for anti-cancer compounds and targeted drug delivery systems. He has 10+ years extensive practical experience in drug development and preclinical studies, both in pharmacokinetics and pharmacodynamics aspects. Previously he worked at the ELKH MTA-SE Pathobiochemistry Research Group, where he gained further experiences in the field of cancer cell biology and signal transduction therapy.

2021 December 1
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New member to the team
We are excited to announce that Márton Megyeri has joined to the team as Head of CMC Development on the 1st of December 2021. He is going to bring a chemistry manufacturing and controls (CMC) and regulatory perspective to the team by managing late-stage research projects of the portfolio. Previously, by leading a team that provided integrated scientific and strategic support for the CMC biosimilar development he completed successful INDs and other regulatory submissions to FDA and EMA. Márton is a bioengineer by training, holds a PhD in structural biochemistry and protein science. He was a postdoc in the Weizmann Institute of Science and held various roles within the biotech industry pipeline. With 9+ years of bio-pharmaceutical experience and 15+ years of academic track record and a passion for science he is going to complete the team’s expertise to cover the full spectra of biologics development.

2021 October 15
Vascular Research Group at the annual meeting of the Peptide Chemistry Association
Vascular Research Group (VRG) presented its progress on CTX analogue development at the annual meeting of the Peptide Chemistry Association (MTA). The annual meeting of the Peptide Chemistry Association (Hungarian Academy of Sciences) took place between 2021 October 11 and 13, and VRG got the opportunity to present its findings for the first time to a wider audience. Following a short introduction of the company and the R&D pipeline, the presentation focused on highlighting completed project milestones on CTX analogue development such as newly designed CTX conjugates which showed improved affinity and specificity to cancer cells. Aside from the talk, we were able to broaden our network in hope for future collaborationsand also the current state of play on peptide research.

2021 September 20
Winning grant support for COMBI-X project
Uzsoki Cardiovascular Center (UCC) had submitted a grant application entitled “COMBI-X: development of a new combination therapy for migraine” (project identification number: 2020-1.1.2-PIACI-KFI-2021-00207) to the Hungarian National Office for Research, Development and Innovation. For the implementation of the project, UCC now received a total of HUF 101,837,282 non-refundable support by the decision of the Ministry of Innovation and Technology. Start of implementation of the project: 16th April, 2021; planned deadline for completion: 16th April, 2024. In this period, thorough concept validation, optimal combination elaboration and preclinical development will be carried out. It is expected that this fixed-combination medicine of two drugs with different mechanisms will allow better migraine prophylaxis than currently available drugs: higher effectiveness than with current therapies, favourable side effect profile and effectiveness in cases of treatment resistance.
2021 September 1
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New member to the team
We are happy to share that Tamás Kitka, PhD joined our team on 1 September 2021 as project and business development manager. He is a neurobiologist with 12 years of experience in pharmaceutical research and development. He was working in original research as a research group leader and project manager at Gedeon Richter Plc. He dealt with animal/human translational issues including model setup, optimizaton/validation, exploratory clinical trial for back-translanslational purposes and also gained experience in launch, evaluation and management of research projects. He gained his knowledge about preclinical development as business development manager of the GLP-compliant preclinical CRO, Aurigon Toxicological Research Center Ltd. where he was responsible for all partners from Central and Southern Europe as well as Middle East, from small biotechs to Big Pharma companies. His duties covered business deals and consulting in various types of preclinical development projects (small molecules, biologics, medical devices, etc.) Thanks to his broad experience, he brings a good overview of the preclinical R&D process from early research to GLP-compliant preclinical development.

2021 August 17
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Why does a single and simple antibody test not give exact information regarding the immunity of the body? Why is a repeated series of testing being better? Why is it safer to also test the immunity on the cellular level too?
– the interview of Portfolio, one of Hungary’s most-read online economic newspapers, with Dr Orsolya Nagy (Vascular Diagnostics’ Laboratory Manager) and Dr Zalán Péterfi (Vascular Diagnostics’ Research Director) gives answers to these important questions. With the brink of the fourth wave of the Covid-19 pandemic on the doorstep by the menacing appearance of the delta-variant, the problem of testing demands a dynamic approach with safe and trustable results. In these times, the question of immunity is more and more relevant. The interview gives a satisfactory answer concerning this issue, presenting a reliable method from the Vascular Diagnostics’ team, that not only dispels the doubts surrounding the antibody approach to identify immunity but also gives a clearer image of how their diagnostic method is safe and sound and why is their company provides a fulfilling career path for the medical experts too in this field.

FIND OUT MROE
2021 July 19
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Variants, vaccination and testing at the dawn of the fourth wave with Dr Zalán Péterfi
The importance of vaccination, the role of testing, and the relation of the variants’ appearance of Covid-19 and the fractionality of vaccination within the society are discussed with Dr Zalán Péterfi, Research Director of Vascular Diagnostics, Hungary’s leading Covid-19 molecular and cellular testing laboratory with over 700 000 evaluated samples and a vast selection of available tests, in the interview conducted by Pénz&Piac, one of Hungary’s best-known economic news site. The problems concerning the pandemic are substantial to everyone nowadays and the expert, Dr Péterfi, expresses his professional opinion to the readers regarding the selection of vaccines and the handling of the virological situation. With the fourth wave of the global crisis caused by the virus, people have to recognize their role in the defence against Covid-19, in other words, the weight of the individuals’ actions in these turbulent times. This and more are reviewed in the interview, providing a perspicuous and informative portrayal of hygienical, virological responsibilities that everyone can take upon themselves to help to combat the pandemical crisis of our modern world.

FIND OUT MROE
2021 June 22
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A new flagship, stepping out into the private sector from 10 years of professional activity in molecular diagnostics – an interview with Dr Zalán Péterfi, Vascular Diagnostics’ Research Director by the Növekedés, a leading journal for Hungarian entrepreneurs.
Competent experience, professional knowledge, and infrastructural preparedness, the triumvirate that describes best Dr Zalán Péterfi’s company, the Vascular Diagnostics, both in the medical field and in the market of diagnostics. The company with 10 years of experience in testing mostly for state orders with molecular methods has accumulated a stable infrastructure, averting the shortage caused by the pandemic concerning medical equipment, and a high-quality human resource, highly trained in medicine and economics from the most prestigious universities around the world, among its ranks, now steps into the field of the private sector to fill the high-demand role of a testing laboratory. Because of this combination, their expertise is ready to show proof to the public of their excellence in the testing and diagnostic for Covid-19 samples. In the interview, Dr Péterfi informs us about why their role in the market is crucial and why their work quality is well above the standard of a sector of which is filled with companies that still try to grasp the how-to of diagnostics.

FIND OUT MROE
2021 May 15
UCC announces launching of COMBI-X project
Uzsoki Cardiovascular Center launched its COMBI-X project aimed at a fixed-dose combination medicine for migraine prophylaxis. The project is based on the discovery of a synergistic effect between two drugs with well-established use in other indications and suppressing also mechanisms involved in pathophysiology of frequent episodic and chronic migraine, conditions of debilitating headache that require preventive treatment. Thus, this project exploits the inventive pharmaceutical research concepts of ’repurposing’ and taking the advantages of beneficial combinations. The preclinical development program was launched in collaboration with a Research Group at the University of Pécs, headed by Prof. Erika Pintér and Prof. Zsuzsanna Helyes, having high reputation in the field of Pain Research.
2021 April 16
We have moved to a new location
We are excited to announce that the VRG-team has moved from our previous location (1022 Budapest, Herman Ottó u. 15.) to a new address near to the city centre of Budapest (1083 Budapest, Füvészkert u.3.). The reason for the move is that the vast expansion of the company’s R&D projects (1 to 6, from 2017 to 2021) requires not only a larger research facility for the equipment but also more room for the grooving team. Our new “home” Research Facility is a renovated 3-story building sitting in the middle of the so-called “Clinics” area in Budapest near to lots of Clinical Buildings and Academic Research facilities. The new Research Building is equipped with the latest technology and the laboratories are custom made to fit our R&D purposes. We believe this “move” will boost up our productivity in the next few years.
2021 April 1
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New member to the team
We are proud to announce Peter Kovács joined our R&D team on April 1st, 2021, as project manager / portfolio manager. Peter has Biology M.Sc., Chemistry B.Sc. and Neurobiology Ph.D. diplomas. Peter has extensive experience in Academic basic research in Hungary (University of Pécs) and in the US, including 4 years as a Postdoctoral researcher at Penn State College of Medicine, resulting in 13 research papers, approximately 100 international congress presentations, 8 awarded grants in Hungary and in the US, including an R01 Co-Investigator role. He worked in the last 12 years in Pharma R&D and Medical Affairs roles at various global pharma companies, including 6 years at Gedeon Richter Plc. And 3 years at GSK, resulting in: 7 launched preclinical drug discovery programs, 2 of which have successfully reached clinical phase, 5 research papers and 1 international patent application. Additionally to his R&D experience, he gained significant expertise in Medico-marketing positioning and driving Healthcare professional (HCP) communication covering a variety of therapeutic areas of Rx and OTC drugs, acting in Medical Advisor, Medical Manager, and Medical Director roles. He has extensive Pharma R&D project management and portfolio management experience, mostly in small molecule Central Nervous System R&D at Gedeon Richter Plc. Finally, Peter possesses significant leadership experiences, including Department Head and Country Head positions in Pharma R&D (4 years) and in Medical Affairs (4 years), including Area Medical Affairs Head position at GSK for 3 years. We believe that Peter’s background and skills will strengthen our Company’s preclinical project management and portfolio management capabilities.

2021 April 1
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New member to the team
We are excited to announce that Attila Brunyánszki, Ph.D., is joining Vascular Research Group as Head of Laboratory on April 1st,2021. Brunyánszki brings his extended cell biology, molecular biology and project lead expertise in peptide-based drug design research and development. He will play an important role in our experimental research, laboratory management, development plan design and extension building new platforms and services.

2021 March 12
UCC announces obtaining the IP rights of COMBI-X
Uzsoki Cardiovascular Center has entered into a contract with the inventors to develop the invention COMBI-X. The project aims to exploit a novel discovery in drug research. The discovery is the recognition of a synergistic effect between two drugs with well-established use in other indications. The discovery was based on an experimental animal model suitable for characterizing the efficacy of drugs for the prevention of migraine attacks. Based on the discovery, it is expected that a fixed-combination medicine of two drugs with different mechanisms will allow better migraine prophylaxis than currently available drugs. The combination product to be developed is expected to be more effective than current therapies, to have a favourable side effect profile, and to be effective also in cases of treatment resistance.

2020 December 31
Vascular Research Group files its first patent application
Vascular Research Group (VRG) successfuly files its first patent protection claim after reaching major project milestonein CTX analogue development. With the aim to develop new chlorotoxin analogues with improved affinity and selectivity for cancer cells, VRGidentified hit molecules utilizing directed evolution through phage display. After demonstrating the new variants’ superior binding to the interaction partner of native CTX, VRG started developing its first lead molecules by implementing rationally designed amino acid mutations in order to synthesizefluorophore and cytotoxic conjugates. As a major milestone, these new conjugates retained their improved affinity and specificity to the target protein. Next, they will be tested in cell based and in vivo experiments. To protect our findings and the developed chemical space we filed in our patent application, and VRG can now proudly present that all 33 claims have been accepted, satisfying the requirements in all three major criteria: novelty, inventive step, and industrial applicability.

2020 December 22
VRG announces winning a Doctoral Scholarship in 2020
Our PhD student, Patrik Szekér of Vascular Research Group submitted and won a four-year doctoral scholarship for the implementation of the Cooperative Doctoral Programme (KDP) in collaboration with the Department of Molecular Biology Institute of Biochemistry and Molecular Biology, Semmelweis University. The Cooperative Doctoral Programme aims to extend the knowledge of the PhD students while making use of their expertise to the benefit of society and the economy. Participants of the programme (grantee, PhD supervisor, corporate expert, doctoral school) receive together approximately HUF 12 100 000 funding per year.
2020 March 23
VRG announces launching of Kv1.3 project
Vascular Research Group launched its Kv1.3 project (Developing a novel, KCNA3 channel specific, autoimmune inhibitor molecule family) aimed to develop selective and sable Kv1.3 inhibitory molecules by a sort of in vitro evolution. There is a huge unmet medical need for less immunosuppressive treatments of autoimmune diseases with diminished adverse effect profile. Kv1.3-channel is currently being considered the main target for treating a range of autoimmune diseases since it is highly expressed in effector memory T-cells (Tem). The overactive and autoreactive T-cells that contribute to the pathogenesis of many autoimmune diseases are mainly effector memory T-cells (Tem), which can thus be preferentially suppressed by selective KV1.3 blockers without affecting naive and central memory T-cells (Tcm) cells. Our technology platform is able to produce and screen a library of a million potential Kv1.3-targeting molecules, for the Kv1.3 channel to select specific Kv1.3 blockers with ex vivo and in vivo proof of concept.

2019 December 12
VRG announces winning grant support for Kv1.3 project
Vascular Venture (VV) had submitted a grant application entitled “Developing a novel, KCNA3 channel specific, autoimmune inhibitor molecule family” (project identification number: 2019-1.1.1-PIACI-KFI-2019-00127) to the Hungarian National Office for Research, Development and Innovation. For the implementation of the project, VV now received a total of HUF 322 219 918 non-refundable support by the decision of the Ministry of Innovation and Technology. Start of implementation of the project: 23rd March, 2020 ; planned deadline for completion: 23rd March, 2023.

2018 January 5
Vascular Venture wins NKFI grant
Vascular Venture (VV) successfuly secures NKFI grant with the aim to develop new, glioblastomatargeting drug candidates. Vascular Venture first R&D project „Development of new MMP-2 selective CTX analogs, targeting MMP-2 overexpressing tumor cells, from scorpion venom” (ID number: KFI_16-1-2017-0524) acquired 493.47 million HUF non-refundable support from the Hungarian National Office for Research, Development and Innovation to pursue peptidebased designer drug discovery. Chlorotoxin (CTX), a small cysteine-rich peptide, isolated from the venom of the Deathstalker scorpion, has been in the focus of peptide based drug development due to its preferential binding to glioblastoma and other type of cancer cells with neuroectodermal origin. Applying directed evolution technology, VV’s ultimate goal is to develop new analogues of CTX with improved affinity and specificity forcancer cells. These new variants would then serve asdiagnostic and/or therapeutic tool. Fluorophore labelled CTX can specifically stain tumor tissues helping surgical intervention, whereas cytotoxic CTX conjugates can hypothetically act as warhead targeting and killing cancer cells only.

2018 January
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New member to the team
Sándor Farkas (MD, PhD) has joined Vascular in January 2018 at the time of foundation of the Research Group, initially as drug R&D consultant, which was later converted to a chief scientist role with full-time engagement. He is a non-clinical pharmacologist and drug developer with 33 years of experience in the pharma industry before becoming a freelance consultant in 2015. Areas of expertise include all phases of early drug development from target identification to non-clinical support of clinical development. He has particular expertise in electrophysiology, safety pharmacology and integrated assessment of efficacy/safety profiles, which was gained by supporting development of numerous drug candidates reaching various clinical stages and some also marketing authorisation. He is author of 38 scientific publications and co-inventor of 23 patent applications, involving 6 innovative drug candidates that reached clinical development.

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