MITCH SAYARE QUOTES @ BIO 2000 3/27/00
"Our first series of products, which is a maytansine, is a very effective agent at killing cancer cells in this targeted way. I want to point out that the technology, we believe, is enabling. There is pretty good evidence that they (DM1)are not detached in the blood. Once inside the cancer cell it is released and the cell dies. Basically, if we can get an antibody inside a cell, using our technology, the cell will die. VIRTUALLY ANYTIME WE HAVE TRIED, THAT'S WHAT HAPPENS. The result is we deliver a very potent agent highly specific to the tumor cell and not to cells that don't over express the targeted antigen. So, high potency, targeted only to the cell, only released inside the cell, results in about a 10,000 fold difference in potency between targeted cells and untargeted cells.
So far in our Phase 1 clinical study we haven't seen any side-effects at all! We presumably deliver high toxicity to the tumor site and I'll show you some evidence to that. Our hope is that this is a NEW PARADIGM by which other agents will be judged. The data that I will show you, albeit in mice (human tumor xenografts in mice) show that the agent has a potential to be CURATIVE! That would be a major step forward in the treating of cancer. All seven animals (mice) that were treated with our agent, starting on day 10 and moving forward for 5 days... THE TUMOR DISAPPEARED AND STAYED GONE FOR THE DURATION OF THE EXPERIMENT SOME 200 DAYS.
In our clinical trial in San Antonio, most of the patients have been colorectal cancer patients. We have dosed a single PANCREATIC CANCER patient and a single non-small cell LUNG CANCER patient. So far we have seen ABSOLUTELY NO EVIDENCE OF TOXICITY WHATSOEVER. We have dose escalated twice, we are at our third dosage level, we have redosed many of the patients, several of the patients more than once and show no evidence of toxicity or immunogenicity. Again, NO TOXICITY. NO IMMUNOGENICITY. So we're pretty pleased with these results.
Turning to our second product, using the same underlying technology, (This product is not yet partnered, we are pretty close to a partnership. This is SMALL CELL LUNG CANCER, the antibody is directed against CD56. In mice, our agent at 60% MTD, well below the level of seeing any toxicity, WE GET CURES IN ALL THE ANIMALS THAT LAST OVER 200 DAYS. (By the way, these antibodies by themselves have no effect in the animals as naked antibodies, none, zero, zip.) Large human tumor xenografts growing in these animals, over 500 cubic millimeters in size, (these are giant tumors) , uh, treating these animals starting on day 25 (of tumor growth) for five days show COMPLETE REMISSIONS and EFFECTIVELY CURES. These animals are sacrificed at 200 days and show no evidence of tumors at all.
When you take a look at what happens when you add TAXOL, which has a modest impact alone, Taxol at MTD plus our agent at 20% MTD you get CURES. This is a result of clear synergy that occurs. They're both tubulin agents (Taxol is a micro-tubular stabilizer, our agent prevents micro-tubular developments). This is something we will take clear advantage of in clinical trials.
These are the sorts of data that I think are pretty compelling in terms of evidence of the underlying technology. They offer a real opportunity for antibodies. I want to explain what this means in the context of our overall strategy. Here we have these TAPs, the first licensed to SBH, we're going forward, we'll speed through this phase 1. SBH begins this phase 1 very shortly, a multi-dose study, and then we'll go into phase 2 and hopefully that phase 2 will be a pivotal study looking for the CURES in the same, or impact in the same patient population as we are treating in the phase 1 studies.
We'll do a partnership with the N901-DM1 I hope within the next couple of months to allow that product to zip through. Even if we don't have a partnership we'll file the IND on that product this summer in the expectation of being in the clinic this fall.
I'm here to talk to you because we believe we have an ENABLING technology here. I've been doing this for 15 years. I've seen a lot of monoclonal antibodies. Most don't do anything when they combine to a cell. In most of the instances I've seen we're talking about incremental improvements in the treatments of disease of 5% or 10%. This technology has the potential to be CURATIVE! You've seen that now in the xenograft model. We won't know if it is in humans YET, but the potential is there.
So, if you have an antibody that is disappointing but gets inside the cell, then we can make that antibody a pretty exciting product using this technology. The genomics revolution has yielded an enormous number of antibodies that offer an enormous number of targets that offer opportunities to make antibodies against them with use of our technology.
Also, maytansines are not the only effecter molecules that we've been using. We have other effecter molecules that are under development that are also capable of killing cells at very low doses.
You have a whole bunch of cancer targets. Targets that may have come from the pharmaceutical industry, that may have come out of academia. People have made monoclonal antibodies against those targets and the result is you have a form of treatment of cancer. There are two out there designed to treat cancer, Herceptin and Rituxan, both of which have demonstrated INCREMENTAL improvements. However, if you're able to take those antibodies from whatever source, and use it as a targeting agent for a maytansine, then your cooking with gas and the potential is great for having CURATIVE products."
Prayin' for the Sayin'
"CURE"
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