8 out of 10 bios were down yesterday and the major index's were down. Today 6 out of 10 bio's were up. Simple recover. I would agree with you if there was high volume but there was not,
Trimesta Deal.A Trimesta Deal is definately eminent at this point and the presentation will create the type of validation and buzz on Friday that will give Riley the type of leverage that will create an auction like setting for the companies wanting to enrich their pipeline. Expect a front end loaded deal that will bankroll roll all the other indications through phase 2 and beyond. Also expect some back end loaded royalties once the drug goes to market in the 12% range along with other milestones during the approval process.
We are like a powder keg and Friday morning a match will ignite the fuse as we count down the days before the Trimesta Deal is announced.
Remember our cash burn is about 1mm monthly and we have enough to get us through year end. Ideally we would like to get this deal done by the end of October as not to dilute shareholder value by having to raise more cash. I think the timing of this presentation plays into this exact plan and a deal will be consumated by no later then the end of October or mid November at the latest..
GO ONCS and SYN
As always, you give great insight. I like Kettle One myself. Like you I am holding strong. Bought and sold earlier in the year and just got back in at .53.
Much of this cancer immunology research has been done at HMS, from the early identification of one of those brakes to later discoveries about how they work. PD-1, CTLA-4 and TIM-3 are three of many proteins acting as receptors on the surface of T cells. They serve as immune checkpoints, and when they bind to their ligands on the surface of other cells, they inhibit T cell responses. Antibody therapies work by blocking this binding process, thereby unleashing the T cells to attack tumor cells
Stephen Hodi, HMS associate professor of medicine at Brigham and Women's Hospital and Dana-Farber, was there at the beginning. His mentor was Glenn Dranoff, HMS professor of medicine at Brigham and Women's and Dana-Farber. Dranoff and Hodi discovered that their tumor cell vaccine worked better when combined with an antibody that blocked CTLA-4, developed by Jim Allison while at the University of California at Berkeley. This led them to the finding that CTLA-4 was a key inhibitor of tumor immunity.
In clinical trials, a drug based on their CTLA-4 work helped some patients with metastatic melanoma live longer, as their tumors melted away. This was the first conclusive work in humans showing that taking the brakes off the immune system could help cancer patients.
Later approved as the drug ipilimumab, this anti-CTLA-4 antibody was the field's first success story in cancer patients who had few other therapeutic options after the tumor had spread. But the therapy came with challenging side effects. Unleashing the immune system allows it to fight cancer, but it also ramps up inflammation in alarming ways. Sharpe had earlier proved how.
Mice engineered to lack the gene that produces CTLA-4 died because their immune systems went wild, clearly showing—by its absence—the power of CTLA-4 as a dominant inhibitor of runaway immune responses. It turns out that CTLA-4 is one of the most important molecules that keep the immune system in a state of tolerance.
"At this point, I've decided that microbes and tumors are the smartest immunologists because they've stolen the tolerance-inducing or inhibitory pathways that are the most important, using them to evade immune eradication," Sharpe said. "A tumor is constantly evolving, so it's able to come up with multiple strategies."
So far, her lab and others have identified more than 10 checkpoints that are active on the surface of immune cells and can be used by tumors to turn off the immune response that should be fighting cancer. One theory holds that these immune cells are suffering from exhaustion, weakened by the constant drain of chronic inflammation or inhibition by cancer cells. Tumors take advantage of this exhausted state, and grow unfettered after they bind to receptors such as PD-1 and CTLA-4 and block the immune response.
Ana Anderson, HMS assistant professor of neurology at Brigham and Women's, working together with her mentor Vijay Kuchroo, the Samuel L. Wasserstrom Professor of Neurology at Brigham and Women's and HMS, identified TIM-3 as another key regulator of immune cell function in cancer. She calls ipilimumab a boon for cancer immunotherapy and is hopeful about drugs aimed at PD-1, but sees opportunities in still other avenues for controlling tumor growth.
"We are getting responses, but we can do better," she said at a recent symposium presented by the Evergrande Center for Immunologic Diseases. "It's important to target other checkpoints."
Keith Flaherty, HMS associate professor of medicine at Massachusetts General Hospital, believes drugs that unleash the immune system are wonderful when they work but inadequate because they work for so few patients. Two out of three patients receiving ipilimumab suffer unintended immune system activation—inflammation in the gut, on the skin or in thyroid, pituitary or adrenal glands—compared to the 1 in 10 who are helped by the therapy.
"That explains why ipilimumab was an advance but not one that made ripples in other cancers," Flaherty said.
Then, in 2010, came experimental drugs to block PD-1. Antibodies directed against PD-1 had a much higher success rate, working in 40 percent of late-stage melanoma patients with a much lower rate of troubling autoimmune, or self-attacking, consequences.
"Forty percent is monumental compared to 10 percent," Flaherty said. "The early and intermediate likelihood of benefit is clearly higher. For the long-term? We are developing that story year by year now."
The anti-PD-1 therapies appear to durably reverse cancer's escape from immune recognition not only in melanoma, but also in other cancer types, such as lung, bladder, kidney, and Hodgkin lymphoma cancers, albeit to lesser degrees. Seven pharmaceutical companies are testing drugs in clinical trials, thanks to a decision made by Sharpe and Freeman to license the intellectual property behind their discoveries widely, allowing many labs to attack the problem.
"Arlene is quite heroic in this regard," Flaherty said. "She and Gordon held some of the therapeutic patents around PD-1, and Harvard and Dana-Farber nonexclusively licensed the intellectual property so all these efforts could multiply. It unleashed a bunch of therapeutic scientists on the problem so people could start engineering different antibodies. Some have worked and some have not, so this is a real blessing."
However promising these anti-PD-1 therapies may be, they may not be enough. TIM-3 antibodies might have advantages over PD-1, which has advantages over CTLA-4. Scientists are betting on combinations of these immunologic kinds of drugs, which then could be doubled up with drugs that target molecular pathways important in cancer development, such as BRAF and MEK inhibitors.
Each agent alone can have powerful effects, but tumors soon find ways around a single agent. Like HIV treatment, where a cocktail of drugs has turned that infection into a chronic illness, combinations of drugs to fight cancer offer more hope than single approaches alone.
"We need multiple drugs at once," Flaherty said. "We and others have built up a portfolio of early clinical trials combining BRAF and PD-1 inhibitors, hoping the BRAF inhibitor will lower the force field and the immune therapies will work even better than they could otherwise."
As an immunologist, Freeman says understanding CTLA-4 was a scientific turning point, while later work on PD-1 was a watershed moment for pharmaceutical development.
"It's amazing," he said about PD-1 therapies. "The PD-1 pathway started 15 years ago as a basic lab discovery and has really taken off. We've cured cancer 50 ways in mice but PD-1 is what works well in people."