New interview with Gary Hudson: developing technologies to fight aging, cancer and other diseases

Oisin Biotechnologies are the result of the hard work of our community of activists, researchers, philanthropists, and many others. Gary Hudson was one of the first to provide funding to the Methuselah Foundation 15 years ago. Oisin's initial funding was provided by the Methuselah Foundation and SENS Research Foundation several years ago. A number of people here, including me , invested in the company at the beginning of last year in order to support this initiative. The initial goal of creating Oisin Biotechnologies was the selective destruction of senescent cells - the implementation of one of the first working therapies for rejuvenating the body as part of the SENS model aimed at eliminating damage . Events are moving fast, as will be discussed below, and Oisin is now participating in a round of fundraising A series to pave the way for human clinical trials.



The SENS approach is to identify and correct the main causes of aging , which are the causes of all age-related pathologies. Cellular aging is one of these reasons: senescent cells usually undergo apoptosis or are destroyed by the immune system, but they accumulate with age. The presence of an increasing number of senescent cells is a side effect of normal metabolism and is a form of damage. Senescent cells generate signaling molecules (SASP) that cause chronic inflammation, arthritis, arthrosis, fibrosis and accelerate the development of many other problems in the functioning of tissues. Removing senescent cells in a safe manner will lead to a significant reduction in degeneration and reverse the change of one of the main markers of aging. It was shown that this approach leads to an increase in life expectancy in mice and reliably improves a number of special markers of aging , reducing age-related pathology.



In one, Oisin Biotechnologies is significantly different from other companies that produce senolithics - drugs that destroy senescent cells. Oisin technology is very adaptive and can be programmed to destroy any cell type that has a distinctive internal marker in the form of a high level of expression of a particular protein. The company's founders initially aimed it at senescent cells, using the p16 marker, but, as can be seen from the above interview with Harry Hudson, they also began to target it at cancer cells using the p53 marker; the use of other markers is only a matter of time, funding and information about the biochemical processes in the targeted cell type. In the long run, technologies are unlimited: any unwanted cells have any distinctive chemical traits that an attack can be set up for, and there are many possible targets.

')

Interview

Risen : Oisin Biotechnologies has been actively working since the last interview for a year and a half, what results have been achieved?



Gary Hudson : I managed to do a lot. In June and August last year, we demonstrated that mice with a normal course of aging (line B6 at the age of 80 weeks) normally tolerate our drug, which significantly reduced the number of their senescent cells in proportion to the dose of the drug. So a single dose reduced the accumulation of β-galactosidase (β-gal) (the recognized marker of aging) in the kidneys by more than 50%, associated with aging , the appearance of the tissues corresponded to animals of about 18 weeks. The decrease in the number of senescent cells was confirmed by real-time PCR analysis.

One of our investors from the Methuselah Foundation suggested that we explore the possibility of using our technology to fight cancer. We had to investigate the possibility of killing tumor cells based on the p53 marker, instead of p16, which was used in the fight against senescent cells. The tests were carried out first on the line of immunodeficient NSG mice , which could not reject human prostate cancer PC3 cells transplanted to their sides. To our surprise, we observed a 90% decrease in the mass of tumors within 24-48 hours after taking the drug. These results are shocking and almost unprecedented.



We repeated these studies in mice with a normally functioning immune system , intravenously infected with a line of aggressive B16 melanoma cells , and showed a decrease in the number of pulmonary metastases by almost 20 times compared with the control group.



Risen : Has the Oisin technology significantly developed since our last interview, taking into account the new focus on cancer in addition to cell aging?



Gary Hudson : Applied technology is evolving, but the key idea remains the same. We have a hammer with which we can wield to destroy cells through apoptosis, and it is quite effective. The choice of specific cells depends on various age-related diseases. So far, we have targeted it to cells based on the expression of p16 and p53 proteins.



It may be useful to remind readers of the essence of our technology. She uses two elements. First, we create a DNA construct that contains a promoter that we want to target. This promoter controls an inducible cell suicide gene called iCasp9 (not to be confused with Cas9 used by CRISPR). Then we encapsulate DNA in a special type of liposome - fusogenic lipid nanoparticle (LNP) . LNP protects the plasmid DNA during transportation through the vessels and allows you to quickly join the cell membrane. The LNP vector is non-selective, it has no preference for senescent cells, it penetrates almost all cell types. After it has penetrated the cell, the plasmid DNA is in the cytoplasm and then in the nucleus. There, it remains in a dormant state, if the cell does not contain transcription factors that are associated with our promoter. If this happens, iCasp9 is activated. iCasp9 is not activated without the presence of a small dimerizer molecule that causes halves of the iCasp9 protein to bind together, which immediately causes apoptosis. This process ensures that other cells are not damaged. So far, we have not observed any effects on other cells.



We also made some improvements both in the part of the promoter and in the part of the effector, which allows us to further expand the capabilities of the technology, but I cannot discuss them until the end of the year for intellectual property reasons.



Risen : The adaptability of Oisin technology seems very important to me. In addition to cancer, what medical problems can be solved by removing certain types of cells. Do you foresee further diversification of the company?



Gary Hudson : We just started exploring more exotic possibilities. But in the list is the purification of abnormal immune cells . No doubt there will be further opportunities as people become familiar with our technology. As I mentioned earlier, we only have a hammer, but it can be very effective and extremely accurate, if you aim correctly.



Risen : If a company with a tempting offer to use Oisin technology appears at your doorstep and asks for a license to use it, will it be interesting for you? Is the role of the hub, which brings together many third-party cell removal projects, an acceptable future for Oisin?



Gary Hudson : Without a doubt. We have already started similar negotiations with several of them and are ready to cooperate with other partners.



Riesen : Did you manage to establish permanent cooperation with other companies and research groups?



Gary Hudson : We negotiated with a number of groups, both academic and industry, and we hope to conclude cooperation agreements with several of them later this year.



Risen : As far as I know, you are now conducting a round of fundraising. How successful is it?



Gary Hudson : We started the round of Serie A and partially completed it. Negotiations have started with “ordinary investors” in terms of filling out applications for participation in this round. Unlike earlier seed rounds that primarily attracted business angels, this round seems to attract investment companies, venture capital, and representatives from the pharmaceutical industry.



Risen : We are all waiting for successful senolithic therapy to be released for clinical trials. When do you expect people to start testing Oisin technology? What steps are still ahead?



Gary Hudson : The next step is a toxicological study. We will begin our first toxicological tests on primates in about 6 weeks and expect results by September. This pilot study will be followed by GLP toxicological tests on various species in accordance with the rules of preclinical testing, which will enable us to begin human trials of phase 1 and phase 2 . We have not yet chosen which indicator we will use in the indicated tests, but it is very likely that this will be prostate cancer . Cancer is a good first marker, as it paves a simpler path to clinical trials than more specific markers of aging. But after completing phases 1 and 2, we will be able to reuse most of the data to facilitate the path to clinical trials of pathologies associated with aging, such as, for example, COPD , atherosclerosis, or liver disease.



Earlier, I mentioned treating animal companions as another possible way for early commercialization, and we have not lost interest in this opportunity, but to heal people is, frankly, simpler (they can remain without movement for several hours during LNP injection) than dogs or cats, which for such a procedure must be subjected to light anesthesia.



Risen : Given your goal of conducting clinical trials as quickly as possible, what do you think about medical tourism and informational transparent research organized by individuals as an alternative to the FDA procedure?



Gary Hudson : This is a tough question. Naturally, we have fiduciary responsibility towards our shareholders and moral obligations towards our patients not to do anything that would adversely affect the chances of getting approval for treating a large number of pathologies in the US and Europe, among other jurisdictions. But it is also true that barriers to entry into the market are hard to overcome for a small company. That is why we are negotiating with potential partners in the pharmaceutical industry, for example, in terms of oncological applications. But we also found that it was easier to work with some western jurisdictions (Canada and Australia come to mind). So, we don’t have to go offshore, in a practical sense, to bring the first drugs to the market. And yet, some regulatory environments will be more favorable to drugs targeting aging than the United States. In this case, we will work with local authorities in accordance with the law to do everything we can to speed up the process of obtaining approval.



Risen : The sphere of senolithic drugs has undoubtedly experienced rapid development over the past few years, and if you ignore the Oisin approach for a second, can you comment on other senolithic technologies and companies?



Gary Hudson : At Oisin, we believe that the healthy senolithic industry requires several different approaches to the problem of cleansing the body of senescent cells. We do not claim that our approach is the best for all types of senescent cells, at least at the current level of science. As for my opinion, I like our “information-based” approach more than small molecules because of the low probability of exposure to other cells. But a successful recovery and rejuvenation of the whole organism is likely to require several complementary drugs.



Risen : How can our community help Oisin at the current stage of research?



Gary Hudson : A public interest in anti-aging therapies should, sooner or later, lead to a policy change. Informing lawmakers about the social importance of work to restore and regenerate the body is the first step towards recognizing the FDA as an illness against which treatment methods can be developed.



In conclusion, I want to point out that SENS technologies are too important to depend only on a small number of our supporters who have dedicated their lives, financial resources and reputation. We need more researchers, companies and funding. Join and do it!

Conclusion

As I mentioned earlier, Oisin Biotechnologies is an example of a near-perfect company in our community, if we look at the long term. To the extent that the project will be successful, a significant part of the profits will be received by individuals who have long been supporters of rejuvenation research conducted by SENS. Thus, it seems to me that a significant portion of the funds received as a result of the success of Oisin Biotechnologies will be re-invested in the financing of the SENS program, aimed at the comprehensive rejuvenation of man. From this point of view, this stage of development of our community - the initial phase of commercialization - is very important. We need to build a cyclical research process with positive feedback funding new research at the expense of profits from previous ones. The closer to our community are the founders and investors, the better it will be for all of us.



Translation done Pattern, SENS Volunteers group