Investing in genome editing
A new approach to the treatment of human diseases based on editing the genome of bone marrow cells is being developed in Russia. At the moment, the developer of the approach – the Russian biotechnology company AGCT (Advanced Gene & Cell Technologies Ltd.) – has focused on its application in the treatment of patients with lymphomas and HIV who require bone marrow transplantation.
The technology is at an early stage of preclinical research and already at this stage was able to attract the attention of an investor: the RBV Capital venture fund, created with the participation of RVC capital and R-Pharm Group, invests 44 million rubles in the development. Last month, RBV Capital and AGCT signed an agreement on the main terms of the investment deal at the Startup Village, the largest Russian startup conference for technology entrepreneurs, held by the Skolkovo Foundation. Marina Popova, General Director of AGCT, tells about what preceded the signing of the agreement and what the allocated funds will be used for.
The idea of treating HIV infection using gene cell therapy was proposed by David Baltimore back in 1988. Scientists around the world have been working on implementing this idea using various technologies for the past 30 years.
"The problem of HIV in our country is urgent and in recent years has acquired the character of an epidemic. At the University, as hematologists, specialists in the field of bone marrow transplantation, we also faced this problem," says Marina Popova about the birth of the project. – At the University clinic, under the leadership of Professor Boris Vladimirovich Afanasyev, director of the R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, more than 3 thousand bone marrow transplants were performed to patients with malignant tumors of hematopoietic and lymphatic tissue, three of them are unique. Three patients with acute leukemia and HIV underwent allogeneic (from a donor) bone marrow transplants."
The story of one of these patients is somewhat similar to the case of the "Berlin patient" who was cured of HIV thanks to a bone marrow transplant from a donor, with a rare change in the CCR5 gene, leading to immunity to the AIDS-causing virus. In Germany, the CCR5 delta 32 aberration in the donor was in a homozygous state – it was in two alleles of the gene. The Russian patient managed to find a bone marrow donor compatible on 10 out of 10 histocompatibility genes with a natural aberration CCR5 delta 32, but located in only one allele (heterozygous state). "The St. Petersburg patient is alive, in remission of acute leukemia, HIV is not detected, he continues taking antiviral drugs," Marina Popova said.
Researchers of the First St. Petersburg State Medical University have been working on the problem of treating HIV and malignant tumors of hematopoietic and lymphatic tissue in this category of patients for the past seven years. According to Marina Popova, the appearance of genome editing tools and scientific papers on editing the CCR5 gene allowed us to take a different look at solving this problem.
"Speaking about editing in general, and the CCR5 gene in particular, it is impossible not to mention the pioneers in the development of genome editing methods for the correction of diseases using zinc finger nucleases (ZFN), the American company Sangamo BioSci. The first work on editing the CCR5 gene under the leadership of Michael Holmes appeared back in 2008. The publication of the first clinical study using CCR5 gene editing in mature human lymphocytes to control HIV and our accumulated experience in the field of hematopoietic stem cell research and bone marrow transplantation, including patients with HIV infection, prompted us to the idea of editing the CCR5 gene in hematopoietic stem cells (bone marrow cells), which has advantages in comparison with editing mature human lymphocytes in order to approach the level of HIV cure, similar to that achieved in the "Berlin patient". With this idea, we came to the OncoBioMed competition in Skolkovo," recalls the CEO of AGCT.
Having won the OncoBioMed competition, AGCT became a resident of the Skolkovo Foundation in December 2015, where the implementation of the idea began. The technology being developed by the company consists in removing the patient's own stem cells from the bone marrow and editing their genome outside the body using TALE-nuclease. The CCR5 coreceptor gene responsible for virus penetration is changed in cells. Cells with the altered gene are transplanted back to the patient, where they differentiate into cells of the immune system and without the CCR5 coreceptor become immune to the most common subtypes of HIV.
"We came to Skolkovo with a scientific idea. It is difficult to overestimate the role of Skolkovo in what happened next. Colleagues from the Foundation actually showed us the way to implement the project, which we had not imagined before. At the same time, everyone participated: a biomedical cluster, an Intellectual Property Center, an Investment Service and, as a result of well–coordinated work, a real startup appeared, which quickly became an investment project of a professional venture fund, - Marina Popova tells about her growth as a resident of the Fund. – For a year and a half, we have received grant and mentor support from Skolkovo. We have worked out a project implementation plan and a business plan. We took second place among the winners of the StartupVillage competition in 2016."
Skolkovo notes the resident's professionalism that deserves support. "Genome editing technologies are certainly a very interesting, promising and rapidly developing direction. AGCT is an example of the synthesis of advanced science, clinical experience and an excellent team," says Vera Rybko, project Manager of the biomedical Technologies cluster of the Skolkovo Foundation. "And we are very pleased to see that such a rapidly growing project has attracted the support of a highly specialized investor."
AGCT has already received the first tranche of financing from the RBV Capital venture fund. According to Marina Popova, the investments of the A-round will be used to prepare a package of preclinical data for conducting a pilot clinical trial of phase 1-2. "The investment strategy implies a gradual reduction of risk. The investments of the first stage will be aimed at completing the “proof-of-concept” research, and additional funding will be attracted to achieve this goal. We expect that the industrial expertise and investments of the RBV Capital fund will allow us to successfully go all the way to the implementation of the technology on the market," AGCT CEO emphasizes. "The developed project development plan provides for the volume of preclinical studies in vitro, iv vivo and the development of technology sufficient to obtain permission for a clinical trial."
If the technology successfully passes clinical trials, its use will save many HIV patients from lifelong antiretroviral therapy, including those resistant to this type of therapy. AGCT carries out research work in cooperation with the First St. Petersburg State Medical University. Academician I.P. Pavlova, participating in the implementation of the National Technology Initiative, works with the Agency for Strategic Initiatives.
The company believes that in the future, genome editing can become the basis for the treatment of other socially significant diseases. But so far, as Marina Popova emphasizes, all the efforts of the team are focused on the first project – the treatment of HIV infection and HIV-associated malignant neoplasms: "Genome editing technology has almost limitless possibilities. To date, this technology can already be used to treat a number of diseases. We have projects for the treatment of oncological and hereditary diseases. But each of them requires significant study, research and investment. Today we are focused on the implementation of our HIV project, and we will return to the rest in the future."
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19.07.2017