- Janssen Biotech, Inc., the pharma unit of industry giant Johnson & Johnson, has broken off a development deal with Maryland biotech Macrogenics, Inc for an early-stage cancer candidate, shutting down a Phase 1 dose-escalation study after treatment-related neurotoxicity was observed in some patients.
- The companies will continue to collaborate on advancing another preclinical molecule based off the same bi-specific targeting platform. Still, Janssen's decision to abandon further work on the more advanced candidate appears to spell the end of the road for that particular program.
- "Given our large portfolio of product candidates currently being pursued, it is unlikely that we will continue development of this molecule at this time," said MacroGenics CEO Scott Koenig in a statement.
Shares in MacroGenics fell sharply on the news, as Janssen's decision raises questions about the promise of MacroGenics' DART platform and cuts short a deal that had over $500 million in milestone payments attached to it.
Janssen and MacroGenics initially teamed up to develop duvortuxizumab, or MGD011, in December 2014 and the pharma partner pushed it into the clinic in July 2015.
Duvortuxizumab is a bispecific antibody designed to target both CD19 and CD3, redirecting patient T-cells to destroy CD19-expressing cancer cells in B-cell hematological malignancies. Janssen saw enough promise in the approach to pay $50 million upfront and invest another $75 million in MacroGenics under the 2014 agreement.
But clinical testing turned up major safety concerns, with an unspecified number of patients experiencing treatment-related neurotoxicity. According to MacroGenics, this safety signal appeared similar to the neurotoxicity seen in other CD19-targeted T-cell therapies.
One such T-cell therapy, Juno Therapeutics, Inc.'s JCAR015, was shuttered after five patients died from cerebral edema due to toxicity related to the CAR-T treatment.
Other CD19-targeted CAR-T therapies, such as Novartis AG's recently approved Kymriah (tisagenlecleucel) and Kite Pharma Inc.'s axicabtagene ciloleucel, have also led to neurotoxicity — although in the case of both Novartis and Kite, the side effects have been much more manageable.
Rapid progress from both Novartis and Kite with their respective therapies also seems to have dulled Janssen and MacroGenics' enthusiasm to push forward with solving the neurotoxicity tied to duvortuxizumab.
"Given the recent advances in the highly competitive field for the treatment of B cell malignancies, the opportunity for development and commercialization has become less attractive," MacroGenics said in a statement on the news.
The companies will continue to work on advancing MGD015, a second molecule Janssen licensed in 2016, into clinical testing. That molecule is also a bispecific, targeting CD3 and an undisclosed cancer antigen in blood and lung cancers.
Janssen plans to begin a first-in-human study of MGD015 in 2018.
Shares in MacroGenics fell by nearly 10% in value to trade at just above $17 per share Friday morning.