OncoSenX is the Oisin Biotechnologies Spinoff Targeting Cancer

Oisin Biotechnologies develops a programmable suicide gene therapy platform, initially used to clear senescent cells from old tissues and thereby produce rejuvenation. Since this approach can also be directed to kill cancerous cells, and with little alteration to the original details of senescent cell targeting, a spinoff company OncoSenX was formed to undertake that line of development. This class of therapy should be broadly applicable to many types of cancer, with little customization required: it currently targets a common mechanism that appears near universally across cancer types.

OncoSenX is a late stage pre-clinical cancer company. OncoSenX targets solid tumors based on transcriptional activity using a unique lipid nanoparticle and plasmid DNA. The next generation in cancer therapies will be more targeted with less side effects. At OncoSenX we believe the battle against cancer should be fought with genetic information. Our treatment delivers a simple program that induces apoptosis in cancerous cells. Our approach is a less invasive, more precise intervention for this complex and devastating disease.

Our system is comprised of two main components: An untargeted non-toxic lipid nanoparticle and a highly targeted DNA payload. DNA plasmids encode an inducible death protein under a promoter that is active in the target cell population. We are initially targeting cells that are transcriptionally active for p53. Cells are killed via apoptosis with caspase 9. We can use our DNA payload to effectively implement logic gates (IF / OR / AND). This allows us to precisely target cell populations based on their genetic activity without harming adjacent cells.

Our patented lipid nanoparticle (LNP) is the transfection agent that efficiently delivers our non-integrating DNA plasmid to cancer cells. These LNPs have been shown to be non-immunogenic, even with adjuvant, and are non-toxic at doses up to 10x expected human therapeutic dose in rodents and non-human primates.

Link: https://www.oncosenx.com/

Comments

It was a logical next step to use the delivery platform for other purposes. From what I read it is almost the same as the senolitics. I get that they want to separate anti aging image from a more conservative , business as usual, biotech, where the tech might be revolutionary but the implications are not.

It was stated several times that LNP platform is not good for Gene therapy, but I don't see why it might not actually be

Posted by: Cuberat at July 26th, 2018 5:49 AM

I feel like I just read the pre-announcement to a cure for cancer. I hope this garners all the right attention and what ever necessary funding flows immediately. It is strange and sad such announcements aren't national news.

Posted by: Tom Schaefer at July 26th, 2018 8:11 AM

>It was stated several times that LNP platform is not good for Gene therapy, but I don't see why it might not actually be

Who say that? For me LNP is the best choise for now. Maybe @Gary clarify?

Posted by: Ariel at July 26th, 2018 9:18 AM

I do not understand this business model of spinning off projects. It would seem to undercut or dilute the interests of investors in Oisin. And I do I understand what is gained by spinning off projects, I would think Brand dilution would be a big downside. And if they continue to work under the same roof allocation of resources is complicated. I am not aware of any Pharma companies that do this.

Posted by: JohnD at July 26th, 2018 9:30 AM

Ariel
> Who say that? For me LNP is the best choise for now. Maybe @Gary clarify?
It was mentioned on the video and somewhere in the comments. Probably they don't want get distracted by extra applications...

@JohnD,
That's weird a bit but probably they want to package each treatment in a separate legal entity, so they can be sold to investors separately. It just don't want to mix approval for cancer and anti-aging...

Posted by: Cuberat at July 26th, 2018 10:30 AM

The purpose of distinct ventures is to separate the complex regulatory process management required for clinical development of specific indications from the discovery focus of Oisin Bio. OB will stay focused upon aging while the spinouts deal with approvals for aging-related indications (or cancer). OB also will control and manage the LNP GMP process to insure quality control of that element.

Spinouts also allow targeting to particular investment pools of funding. OB investors own an interest in each spinout though their OB ownership.

Another company following a similar strategy is Ichor.

Posted by: Gary at July 26th, 2018 11:10 AM

@Gary
Hi Gary,
Can you tell whether the ok lipid delivery platform can be used whith genetic therapy payloads?

Thanks

Posted by: Cuberat at July 26th, 2018 11:29 AM

@tom Schaefer: It sure sounds like they may have a real cure for a bunch of cancers. Think I will look into it and pick some shares up. Thanks for calling it to my attention.

Posted by: Biotechy Marcks at July 26th, 2018 11:46 AM

@Cuberat - Oisin are probably reluctant to speculate on whether their Lipid Nanoparticles can be used for non suicide gene therapy until the LNPs have actually been tested in people.

Cancer is the obvious first target as "if it bleeds it leads", the public care more about diseases that kill them, rather than just put them in pain, and so politicians care more, and regulators focus more of their resources on approving treatments for these diseases.

Posted by: Jim at July 26th, 2018 11:53 AM

A speculative question I have is - could OncoSenX's LNP platform be adapted to target commonly mutated proteins such as KRAS? I don't think they'd just be able to insert a genetic program that activates suicide if a promoter is active, as non mutant KRAS is expressed in non cancer cells.

But perhaps they could express something like Ichor's RecombiPure Tags, which are small antibody like proteins reputedly stable in the cell cytoplasm, which could detect mutant KRAS proteins and then activate a suicide protein?

Posted by: Jim at July 26th, 2018 12:24 PM

The LNP can carry various payloads, from nucleic acids (DNA/RNA) to proteins, or peptides, or small molecules. Oisin has license to employ certain of those payloads, while our partner Entos retains rights to other payload (such as small molecules).

Posted by: Gary at July 26th, 2018 1:00 PM

"The LNP can carry various payloads, from nucleic acids (DNA/RNA) to proteins".

Ok, interesting, so in theory you would not even have to include a plasmid for an RP Tag, you'd just stick the protein directly in a LNP and deliver that to cells.

LNP technology really does sound like something of a holy grail. I hope it doesn't hit snags in human testing.

Posted by: Jim at July 26th, 2018 1:18 PM

it does, would be interesting if it could deliver whole cellular components such as mitochondria, whole chromosomes, lysosomes, or ribosomes

Posted by: Chris at July 26th, 2018 2:11 PM

@Chris - Mitochondria are a lot bigger than an individual protein. I'm just a layperson, but that sounds like a stretch.

Posted by: Jim at July 26th, 2018 3:06 PM

@Chris,Jim
In theory, the payload could be an RNA with sequences to assemble its own, probably alien organelles. This way , turn the LNT into a pseudo virus, which can alter the cell behavior on all possible ways. However, I am afraid, that works require many orders of magnitude improvement of our knowledge and technologies...

Posted by: Cuberat at July 26th, 2018 8:41 PM

@Jim: Cells apparently take up whole mitochondria with comparatively little effort or coercion needed. Someone demonstrated that a few years back. Distribution to the tissues of interest is probably the bigger challenge.

Posted by: Reason at July 27th, 2018 12:36 PM

@Chris, Reason - This is getting very speculative and off topic, but if you can use nanobots to deliver cells to hard to reach organs, you can probably do the same for mitochondria:

https://spectrum.ieee.org/the-human-os/biomedical/devices/tiny-robots-deliver-stem-cells-in-the-body

"A group out of Hong Kong announced this week that they had invented a new delivery tool using tiny, magnetically-controlled robots. The cell-carrying machines move noninvasively through the body to a target site and deliver their stem cell cargo.

The researchers, led by Dong Sun, a professor at City University of Hong Kong, demonstrated their device in zebrafish and mice, and reported their success in the journal Science Robotics.

The advance is notable because Sun and his colleagues were able to demonstrate that their robots work in animals. "It's really uncertain how to make these tiny machines move in living organisms," says Bradley Nelson, a microroboticist at ETH Zürich, who was not involved in the project.

Several other groups, including Nelson's, have demonstrated cell-carrying microbot designs in computer simulations and test tubes, but "in vivo is harder," he says. "

Posted by: Jim at July 27th, 2018 2:36 PM

Very exciting. I definitely expect something like this to be the way forward for cancer treatment. I never really liked the idea of the SENS "WILT" model of removing telomerase from the entire body. It seemed too much like taking a sledgehammer to a walnut.

Posted by: Link at July 27th, 2018 5:07 PM

Gary, could OncoSenX tech be conceivably used to kill pre-cancerous mutant cells and thus prevent cancer? It seems that OncoSenX proposes for it's LNP/DNA construct to enter all cells and kill only cancer cells. And perhaps the construct could be repurposed to kill mutant cells too.

Posted by: Florin Clapa at July 27th, 2018 6:08 PM

@Florin Clapa: We have certainly considered this option, and it will be something we will look at in more detail when we can afford the resources to do so. It is possible to target any promoter, or combination of promoters, so if such are identified, the cells could be ablated.

Posted by: gary at July 27th, 2018 7:16 PM

If the LNPs can carry RNA, then there is very little limit to what you can do in cells. Quite exciting.

Posted by: Mark at July 29th, 2018 2:05 AM
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