CTL-119

June 1, 2017 By Mark Terry , BioSpace.com Breaking News Staff After rumors that Tesaro might be acquired that have been flying for over a year, it appears that the Waltham, Mass. company is officially up for sale . But inside sources say interest in the oncology company have been lukewarm. On March 27, the U.S. Food and Drug Administration (FDA) approved the company’s Zejula (niraparib) for maintenance treatment of women with recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. The drug is a PARP inhibitor, the first to be approved by the FDA that doesn’t require BRCA mutation or other biomarker testing. Most analysts believe Zejula has blockbuster potential. With another product on the market, Varubi (rolapitant), a drug to help with nausea and vomiting caused by chemotherapy, and a promising pipeline, why aren’t companies interested? The most likely reason is price. The news has made the company’s stock climb 4 percent, giving it a new market cap of about $8 billion. This makes it out of reach of many companies. Pfizer (PFE), a company large enough to acquire Tesaro and with a taste for acquisitions, already acquired its own late-stage PARP (talazoparib) inhibitor when it acquired Medivation for $14 billion, a price most analysts think was inflated. John Carroll, writing for Endpoints News , says, “Competition from a bullish AstraZeneca and Clovis won’t make it any easier. J&J )has already licensed rights for prostate cancer, its core interest.” And Carroll notes that Roche has promised to avoid an acquisition such as Tesaro. Many companies are waiting to see how the Trump tax plan and overseas repatriation proposals shake out before jumping into big acquisitions. He writes, “ Gilead has an interest in cancer therapies, but so far has refused to pull the trigger on a big one. Sanofi has been satisfied with second place in at least two bidding wars for Medivation and Actelion . It won’t want to pay unlimited sums to buy what it wants, but that could always change.” In February, it was rumored that Sanofi was in talks with Tesaro. Others suggested as potential acquirers were Amgen and Celgene . Tesaro has about 430 employees, with 300 of them located in Waltham, Mass. One possibility for a buyer is Novartis . Yesterday the Swiss company announced dazzling findings on its mid-stage trial of CTL119, a CAR-T therapy, in chronic lymphocytic leukemia (CLL). And the day before, there was talk of the company’s potential plans to sell off some of its largest assets, including U.S.-based eye care company Alcon (ACL). The total of the sales, if they came to pass, would be about $50 billion. Plenty of cash to acquire Tesaro, and the company is lagging behind in the immuno-oncology market. But analysts with Leerink recently sat down with Novartis’ executives to discuss its pipeline, and seemed to shoot down the possibility of a Tesaro acquisition. Leerink’s Seamus Fernandez wrote, “Novartis acknowledge that the lack of a PARP inhibitor was a gap in its oncology portfolio, but commented that valuations were too high to justify a major deal in the space.” Although, who knows? Companies don’t like to share their M&A plans unless it’s strategically advantageous. Tesaro is currently trading for $147.08.

May 31, 2017 By Mark Terry , BioSpace.com Breaking News Staff Switzerland-based Novartis announced findings from a pilot study of CTL119 that had dazzling results. CTL119 is a CAR-T cell therapy, where T cells that express chimeric antigen receptors (CAR) are engineered to target any cancer antigen desired. In the early study, nine patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who had been on Imbruvica (ibrutinib) for at least six months, but were not in complete remission, had CTL119 added to their therapy regiment. In three months, eight of the nine patients showed no signs of CLL in their bone marrow. One of the patients had a partial response. There were a total of 10 patients in the study, but one did not produce data that could be evaluated. “The data from this pilot study support the potential for CTL119, when combined with the kinase inhibitor ibrutinib, to induce clinically-significant responses in high-risk CLL patients who were unlikely to achieve a complete remission on ibrutinib alone,” said James Bradner , president of the Novartis Institute for Biomedical Research , in a statement. “CTL119 represents one of our latest advances in CAR-T cell therapy research and our broader commitment to pioneering breakthrough immuno-oncology treatments.” John Carroll, writing for Endpoints News , says , “The work at Novartis reflects a commitment from all the lead players that the first wave of CAR-Ts—including KTE-CD19 (axicabtagene ciloleucel) from Kite Pharmaceuticals —can be improved on with new technology. But it’s even more important for Novartis, which is out to demonstrate that it is completely committed to developing novel waves of CAR-Ts.” Although the Novartis study had amazing results, it was not without the complications that have marked almost all CAR-T efforts. The small study had at least two serious cases of cytokine release syndrome (CRS). CRS is common with many monoclonal antibodies and is otherwise referred to as an infusion reaction. Per Breslin S in “Cytokine-release syndrome: overview and nursing implications ,” “it results from the release of cytokines from cells targeted by the antibody as well as immune effector cells recruited to the area. When cytokines are released into the circulation, systemic symptoms such as fever, nausea, chills, hypotension, tachycardia, asthenia, headache, rash, scratchy throat, and dyspnea can result. In most patients, the symptoms are mild to moderate in severity and are managed easily. However, some patients may experience severe, life-threatening reactions that results from massive release of cytokines.” These are sometimes referred to as “cytokine storms.” Novartis indicated that all 10 patients in the study experienced CRS. Two of them were grade 3. However, no patients required treatment with Roche (RHHBY)’s Actemra, a drug that minimizes the response. All of the patients recovered from CRS. One patient also developed tumor lysis syndrome. Two patients had febrile neutropenia. Saar Gill , an assistant professor of Hematology-Oncology at the Perelman School of Medicine and the Abramson Cancer Center of the University of Pennsylvania , will present the findings from the study at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) on Monday, June 5 at 1:15 PM CDT. It was just reported yesterday that some investors are nervous about Novartis’s business plans. The company is considering selling off some of its largest assets, including U.S.-based eye care company Alcon (ACL). The total of the sales, if they came to fruition, would total about $50 billion, and some investors worry that Novartis will buy something large that won’t help the company as much as smaller deals. One of the concerns about Novartis is that it’s lagging in the immuno-oncology market behind competitors Roche , Merck and Bristol-Myers Squibb . However, if the company can get a successful CAR-T therapy to market, especially if it can beat Kite Pharmaceuticals , some of those concerns may be assuaged.