In this video from Motley Fool Live recorded on Nov. 12, executives from Sorrento Therapeutics (SRNE 11.11%) talk about the company's second-generation therapeutic antibody. An investigational new drug (IND) application has been submitted to the Food and Drug Administration.
Mark Brunswick, senior vice president of regulatory affairs at Sorrento, talks about how much better STI-2020 (COVI-AMG) is than the first-generation version STI-1499 (COVI-GUARD). And Henry Ji, Sorrento's chairman, president, and CEO, highlights a third-generation version that uses DNA to express the antibody inside a patient's cells.
Brian Orelli: Moving onto STI-2020, what you also called COVI-AMG, it's a next-generation version of COVI-GUARD. Please talk about the pre-clinical data that showed how much better STI-2020 is than its predecessor.
Henry Ji: Yes. Okay. Go ahead, Mark.
Mark Brunswick: In vitro, what we did was we took 1499 and we made it into a better antibody. We then tested that antibody in an in vitro infection assay, and it was 80-fold better than the parent antibody. When we tested that antibody in a hamster model, it was at least fourfold better, probably more, but we didn't have good titration data, but it was enough to take this forward to show that we're now going into people with a dose that we anticipate to be in the order of a treatable dose of about 100 milligrams per patient. [Eli] Lilly's (LLY +10.01%) EUA is for 700 milligrams, Regeneron [Pharmaceuticals] (REGN +3.00%) are using eight grams antibody.
Brian Orelli: When do you expect to be able to get into the clinical trials for the second-generation antibody?
Mark Brunswick: The IND for the IV injection and intranasal was submitted this week. The FDA typically has 30 days to review before those trials will go ahead. But since this is so similar to 1499, we're hoping that they will review quicker because they are very familiar with the data already.
Brian Orelli: Why not just move on with STI-2020 and put COVI-GUARD, the first generation antibody, on the back burner?
Mark Brunswick: Because we will get information on the parent antibody while the FDA is reviewing that data.
Henry Ji: Brian, the idea is if we get the testing going with the 1499, that give us an estimate what is the potency, what is the dosing needed? Then you calculate what the improved version we have. That will give us instantly the ideas how good the 2020 or the intranasal going to be. With that data in place, we can do very quickly, move very quickly with the 2020 and the intranasal application of the neutralizing antibody.
Brian Orelli: Then you're also developing a treatment that would express STI-2020, that antibody, in patients off of the DNA. What's the advantage there over just treating directly?
Henry Ji: Yes. I am glad, Brian, you're asking. We acquired a company, CosmoFarm, it's Boston-based. That actually come with the encoded plasmid DNA technology and utilizing plasmid DNA, expressing the most potent antibody in the muscle. We'll be able to have the body generate the antibody itself. Now, the antibodies are defined, it's not random like random antibody from immunization of vaccine. This is totally defined.
In a simple layman's term, you have a vaccine generate antibody, hopefully that's neutralizing the virus but does not cause the side effect. Then you have a bad antibody, they create the antibody-dependent enhancement, and the useless antibody, the antibody only binds to the virus, but does not do a whole lot. So by doing defined, only good antibody get expressed through the encoded DNA plasma that are in your muscle. You control the side effect. You control what's the dosing you needed.
For example, if you need a certain dosing, we know from our IV injection what is the dose you needed. You can always apply and you can measure what's the diagnostics like a COVI-TRACK to measure it. What's the quantity you have? If your missing some quantity, you can always inject a little bit more of the plasmid DNA. Let the body generate itself. Now, in this case, you are like vaccine. The application is like a vaccine. You can produce tons of plasmid DNA. We're talking about hundreds, millions, if not billions of doses, and they have the body produce itself. That antibody is defined, there is no side effect, cannot be controlled. Like a vaccine, you cannot control the side effect because you don't know whose body generated some bad antibody. But in this case, you have only defined antibody with no ADE because it's all engineered out. You have a defined antibody. You have a massive production. Also, plasmid DNA is very stable. You can store in room temperature for years to come and you can put it in the refrigerator so the [...] logistic is all totally avoided. You can apply anywhere, you can ship anywhere, FedEx Express, anywhere, and that's [...]
Brian Orelli: What's the timeframe for getting the DNA-based treatment into the clinic?
Henry Ji: Brian, what we did is firstly, we built a cGMP facility for making the cGMP material, which is a plasmid DNA, also the formulation. We right now have the plasmid DNA and we have the formulation. Now, we need to just produce cGMP and then do a PK study so then know how much quantity you needed. We have from our testing IV like COVI-AMG, we should get the PK data. So we know which quantity in your body going to work. Then we're going to just titrate the plasmid DNA in a muscle. We can control the expression level to meet the effective dose from a pure antibody IV infused. With that in places, going to be able to do testing. Initially, maybe it was infected people and see whether we can reduce the symptom immediately. Then you get to prevention. If that prevent the infection of preventing the seriousness of the disease, then we can starting talking about a vaccibody. The vaccibody means it act like a vaccine, however, is an antibody. You can produce massive quantity, for hundreds million, maybe billions doses that act like a antibody but avoiding all of the pitfall with the vaccine. That's the thinking behind our approach.
Brian Orelli: How quickly can you get into the clinics? Have you done pre-clinical data with this approach yet? Do you have animal data yet?
Henry Ji: We have to produce the cGMP material, we're in the middle of doing that. As you know, while we're very good with the animal data, we have hamster challenge datas, so these we generate. We envision in the next couple of months, we should be getting all the package in places and submit it to the FDA if that works. If the FDA likes it, we can get into human immediately. It's your next-generation vaccine. The beauty of this one is if this works, every time you have a new strain comes in, we can have a new antibody or mutated. The engineered antibody works on a variance and we can immediate put into plasmid DNA and get it done immediately. I think it's a game changer here.
