Marizomib

mistydawnphoto / Shutterstock.com McCain died Saturday after deciding to discontinue treatment for brain cancer. He approached the end of his life in the same manner in which he approached me that day in Raleigh – with the strength of character. mistydawnphoto / Shutterstock.com Long before Sen. John McCain was diagnosed with brain cancer, I got the chance to briefly meet the man who developed a reputation as a maverick in the Senate. It was in Raleigh, N.C. about 12 years ago, and he was in town pushing for support of public financing of judicial elections in the Tar Heel State. I was a political reporter with The Wilson Daily Times (now The Wilson Times ) and covered McCain’s push for the plan, something for which he was a proponent. After the presentation, I got to spend a few minutes with the senator. I don’t recall the details of the conversation, only the kindness and character-defining way in which he treated me and all the reporters in the room. Although I no longer write about politics, I (sort of) crossed paths with Sen. McCain last year after he revealed he had been diagnosed with brain cancer. McCain died Saturday after deciding to discontinue treatment for the cancer. He approached the end of his life in the same manner in which he approached me that day in Raleigh – with the strength of character. When McCain revealed his brain cancer last year, BioSpace pointed to 10 companies that were in pursuit of treatments for glioblastoma , the most common form of brain cancer and one that is highly aggressive. The disease is somewhat rare, impacting only about three out of every 100,000 people in the United States. Although it’s a rare disease, companies are still chasing after a potential treatment. Citing the National Institutes of Health (NIH) , CNN reported there are currently 274 glioblastoma multiforme studies underway or recruiting across the United States. One early-stage treatment has been receiving some press due, primarily, to one patient who has shown a remarkable response to the treatment. Bob Rulli, a retired airplane engine designer, was diagnosed with glioblastoma multiforme five years ago. He has been a clinical patient of startup Bexion Pharmaceuticals . Rulli has been undergoing treatment with BXQ-350 , a formulation of a synthetically produced, human lysosomal protein, Saposin C (sphingolipid activator protein, or SapC), and the phospholipid dioleoylphosphatidylserine (DOPS). Average life expectancy is less than two years. Rulli has been on the Bexion treatment for 19 months. His cancer hasn’t been eliminated, but the tumor has proven to be stable during that time. BXQ-350 is currently in Phase Ia. Earlier this month AiVita Biomedica l initiated its first clinical site for the ROOT OF CANCER Phase II trial in patients with newly diagnosed glioblastoma. Patients will receive autologous dendritic cells loaded with autologous tumor antigens derived from self-renewing tumor cells as an adjunctive therapy following primary surgery plus concurrent chemoradiation, the company said. In April, China-based CANBridge Life Sciences announced plans to initiate its Phase II/III glioblastoma multiforme trial following the nod from the China Food and Drug Administration. The company’s lead candidate, CAN008 is a “fully human fusion protein that inhibits the CD95 ligand, a member of the tumor necrosis factor (TNF) family,” according to company data. By blocking CD95, CAN008 “restores the immune system’s anti-tumor response and inhibits invasive cell growth,” the company said. In December 2017, Virginia-based Diffusion Pharmaceuticals initiated a Phase III trial for its lead glioblastoma product, a small molecule trans sodium crocetinate (TSC). Phase II results showed that in an inoperable patient subgroup, the led candidate helped them achieve a “nearly four-fold increase in survival compared with historical controls when TSC was added to their treatment regimen,” the company said. Data showed that 40 percent of the patients were alive at two years vs. 10.4 percent. In 2016, Celgene acquired marizomib, a novel, brain-penetrant proteasome inhibitor. The company is developing the therapy as a possible treatment for patients with newly diagnosed glioblastoma. The therapy is entering Phase III. Last year Inovio and Regeneron partnered on a brain cancer study . Inovio will pair two of its investigative products, INO-5401 T cell activating immunotherapy encoding multiple antigens and INO-9012, with Regeneron’s PD-1 inhibitor, REGN2810. There have also been some setbacks with glioblastoma research. ZIOPHARM Oncology announced a delay this spring in its planned Phase III glioblastoma treatment , Ad-RTS-hIL-12 plus veledimex. The company is developing a gene therapy product designed to treat patients with recurrent glioblastoma (rGBM) as a monotherapy and in combination with an immune checkpoint inhibitor. In May the company announced it had to delay the trial in order to resolve technical requirements related to Chemistry and Manufacturing Control (CMC). This was the second delay for ZIOPHARM’s study.

Pfizer is no stranger to taking the big gambles-note the company’s attempts to buy Astra in 2014 and Allergan in 2016. Pfizer is no stranger to taking the big gambles—note the company’s attempts to buy AstraZeneca in 2014 and Allergan in 2016. The company has made some significant acquisitions , such as Hospira for $17 billion and Medivation for $14 billion. But nothing has quite touched the scale of the AstraZeneca and Allergan takeover attempts. But Keith Speights, writing for The Motley Fool, makes an argument that Pfizer should—or could—take another swing for the fences, this time for Celgene . Based in Summit, New Jersey, Celgene is a big player in the oncology market. It is also noted for its numerous collaborations and partnerships. It has a market cap of around $80 billion, which would make it an expensive company to buy. Pfizer, as of Oct. 1, had about $17 billion in cash with $44 billion in debt. It could probably buy Celgene, but it would be a tough financial nut to crack. So why does Speights think it would be a good idea? Even though he recognizes that it’s a crazy idea. Three reasons. First, Pfizer is being battered by patent expirations and its earnings haven’t been all that impressive in recent years. Celgene, however, is expecting sales growth of 14.5 percent annually through 2020. Speights writes, “Buying Celgene would boost Pfizer’s growth significantly. Pfizer is on track to generate revenue of around $52 billion this year. Celgene’s revenue should hit at least $19 billion by 2020, up from roughly $13 billion in 2017. The most impressive change, however, would be on Pfizer’s bottom line. The company will probably earn around $12 billion this year. Celgene should make close to $9 billion in net income three years from now.” Secondly, it’s a good fit. Pfizer wants to expand its presence in oncology, and already has a couple hot cancer drugs, Ibrance and Xtandi. But its Sutent is slowing. And recently, along with Merck KGaA , there were setbacks for Bavencio in a late-stage trial in gastric cancer. Speights notes, “An acquisition of Celgene would bring a boatload of current and potential blockbuster cancer drugs into Pfizer’s fold. There is little overlap between the two companies’ portfolios and pipelines in hematology. It’s a different story in solid tumors, since Celgene has Abraxane. However, Pfizer would probably love to have Celgene’s experimental glioblastoma drug marizomib and CC-486, which targets treatment of metastatic breast cancer and non-small cell lung cancer, in its arsenal.” Thirdly, the timing is right. Celgene’s price would be a little lower now, after investors panicked over the pipeline setback of GED-0301. And, as Speights notes, although it’s possible that Congress’s tax plan won’t make it through the gauntlet, given its overall lack of popularity with the U.S. public, if it does—which is likely—there’s a big change in corporate taxes coming. And Pfizer has a ton of cash trapped overseas, which it would be able to repatriate at a lower tax rate if reform goes through. Speights writes, “I think it’s obvious that Pfizer is itching to do something big. As alluded to earlier, the company tried to buy AstraZeneca for $118 billion three years ago. Pfizer scuttled its plans to acquire Allergan only after the U.S. government changed policies that minimized any tax benefits from the deal. Pfizer’s executives recently stated that they’re ‘agnostic to size’ when making acquisitions, which could be interpreted as they’re not afraid at all to make yet another attempt for a big takeover.” A Bristol-Myers Squibb acquisition is more likely, and Pfizer and BMY have a partnership over blood thinner Eliquis. But Celgene would be a stronger growth prospect, especially in oncology.