March 30, 2015
By Riley McDermid, BioSpace.com Breaking News Sr. Editor
The race to achieve the smartest, most effective Chimeric Antigen Receptors T-cell therapy (CAR-T) heated up Monday, as Merck Serono said it would fork over $115 million upfront payment along with a commitment of up to $826 million more in milestones to new partner Intrexon Corporation as it looks to enter the cutting edge oncology fray.
CAR-T cells are genetically engineered T-cells with synthetic receptors that recognize a specific antigen expressed on tumor cells. When CAR-T cells bind to a target, an immunological attack against the cancer cells is triggered.
Merck Serono, the research and development arm of the German drugmaker, will now have access to Intrexon‘s CAR-T tech, a significant part of which was recently in-licensed from the University of Texas MD Anderson Cancer Center.
“The collaboration with Intrexon underlies Merck Serono‘s focus on innovation, and enhances its R&D technology portfolio in immuno-oncology,” said Belen Garijo, president and chief executive of Merck Serono, in a statement. “Moreover, it showcases Merck Serono‘s commitment to developing therapies that have the potential to significantly evolve the way cancer is treated.”
Merck will now join both Big Pharma companies and smaller, scrappier start-ups like Juno Therapeutics in a long line of gene therapy biotechs focusing on T Cell Receptors (TCR) and Chimeric Antigen Receptors (CAR) and include chimericantigen receptor drug candidates, For example, Juno alone has three potential candidates, JCAR 014, JCAR015, and JCAR017, while in December Pfizer Inc. inked a $2.85 billion partnership with Merck KgaA on a preclinical PD-L1 oncology deal.
They are getting in just in time, say some market watchers. Wall Street analysts who attended the 5th Annual Cancer Immunotherapy: A Long-Awaited Reality last week conference came away feeling that the emergence of checkpoint inhibitors and CAR-T over the last several years is only the tip of the iceberg for immunotherapy, said Boris Peaker, a biotech analyst with Cowen and Company in a note Friday.
Peaker said there was “plenty of discussion” around checkpoint inhibitors, with the keynote speaker noting that there hasn’t been an indication/histology that hasn’t responded to anti-PD-1/PD-L1 therapy.
“There was lots of focus on finding biomarkers to predict responders, understanding why patients fail anti-PD-1/PD-L1 therapy, and what other agents will best complement PD-1/PD-L1 agents,” wrote Peaker in a note to investors. “Numerous panelists noted that mutational load and quantity of tumor infiltrating lymphocytes have shown to correlate somewhat with response, but conceded that better approaches were needed.”
Peaker also noted the concern from attendees about converting patients with poor T-cell infiltrate into T-cell inflamed tumors to sensitize to PD-1 blockade. “Panelists also noted that while CTLA-4, PD-1, PD-L1 are currently the primary focus of checkpoint inhibitor therapy, there are 100s of other targets (co-stimulatory and co-inhibitory) within the T-cell checkpoint pathway and that many more viable targets will emerge,” said Peaker.
Above all, however, CAR-T therapies captured the spotlight yet again. There were two main areas of focus surrounding CAR-T cell discussions which included improving the current CD19 CAR-Ts and identifying suitable antigens for solid tumors.
One presentation spoke to the poor response rates that have been observed in CLL compared to ALL. One reason might be the tumor microenvironment of CLL, “specifically regulatory T-cells,” said Peaker.
“One presentation discussed the next generation of CAR-T cells that will be constructed to express the CAR/TCR, as well as the IL-12 cytokine to modify the tumor microenvironment. In regards to solid tumor antigens, there was a clear consensus among panelists that there was no CD19-like antigen at the moment.”
