CEO: Ying Huang
Legend Biotech was that dark horse we spotted at 2017’s American Society of Clinical Oncology annual meeting.
While industry watchers were watching the CAR-T battle between Novartis and Kite Pharma, now part of Gilead Sciences—while also keeping their eyes on Juno Therapeutics and bluebird bio, whose candidates are now both housed by Bristol Myers Squibb—Legend splashed onto the scene.
Early-phase data from China showed 33 out of 35 heavily pretreated multiple myeloma patients saw their tumors shrink after receiving Legend’s anti-BCMA CAR-T drug, LCAR-B38M—including 15 who had no remaining signs of cancer after treatment. Of the 19 patients who were followed for more than four months, 14 saw stringent complete responses, and all responded to treatment.
At the same event, bluebird bio shared data for its Celgene-partnered bb2121, now called ide-cel, in 18 myeloma patients who had received a median seven prior treatments. The company reported an 89% remission rate, with four complete remissions. It was an impressive readout, yet one totally upstaged by Legend.
Both ide-cel and LCAR-B38M target BCMA, while Novartis’ Kymriah, Gilead’s Yescarta and Bristol Myers Squibb’s investigational liso-cel are CD19-directed CAR-T drugs.
Legend believes its drug is differentiated because of its unique CAR construct. Designed with a bispecific antibody platform, LCAR-B38M binds to two key BCMA sites on tumors through a mechanism that Legend chief scientific officer Frank Fan compared to grabbing a ball with two hands. This allows tighter binding that makes it much less likely for cancer cells to escape.
The data turned heads, and among them, Johnson & Johnson’s. Six months later, the U.S pharma paid $350 million upfront for ex-China rights to LCAR-B38M, now also known as JNJ-4528 or cilta-cel.
In an update from the phase 1/2 Legend-2 study at 2018’s American Society of Hematology annual meeting, among 57 Chinese myeloma patients who had previously failed a median of three prior lines of therapy, the drug achieved an 88% overall response rate—with 74% seeing their cancer completely cleared—after a median follow-up of 12 months.
Like many other cancer treatments, patients on CAR-T might relapse even after initial remission. Of the 42 patients who had a complete response, 39 of them (68%) tested negative for minimal residual disease in their bone marrow, suggesting they were less likely to experience a relapse than those with higher levels.
That kind of showing was largely replicated in the Cartitude-1 phase 1b/2 trial carried out in the U.S. and Japan among patients who had failed on a median of five prior regimens. In the phase 1b portion, the drug shrank tumors in all 29 patients and kept cancer at bay in 25 (86%) after a median follow-up of 11.5 months, according to data presented at this year’s ASCO virtual event.
In comparison, updated ide-cel data at this year’s ASCO showed the drug shrank tumors in 73% and cleared signs of tumors in 33% of patients who had tried a median of six prior therapies after a median follow-up of 13.3 months.
Ide-cell will likely reach the market sooner, with an FDA decision in relapsed or refractory multiple myeloma set for March 27, 2021. Enrollment into the phase 2 portion of Cartitute-1 has wrapped up, and J&J has said it intends to file for approval this year, while Legend plans to submit for Chinese approval in 2021 based on data from a China-specific phase 2, dubbed Cartifan-1.
Riding on positive ASCO data, Legend landed on the Nasdaq in an upsized, $424 million IPO in June. But it was unexpectedly distracted recently. In August, Yuan Xu, who took Legend’s reins in March 2018 after leading Merck Research Laboratories’ biologics & vaccines subdivision, resigned. Frank Zhang, Legend’s chairman and CEO/founder of its parent company, Chinese CDMO giant Genscript, took over as CEO.
But less than two months later, Legend unveiled that Zhang had been put under residential surveillance by Chinese law enforcement. The custodial measure came after China’s Customs Anti-Smuggling Department raided Genscript’s businesses in the cities of Nanjing and Zhenjiang, including Legend’s office. No formal charge has emerged thus far, and Legend has said its operations were not interrupted.
Ying Huang, Legend’s chief financial officer since July 2019, first became interim CEO and has adopted the title permanently on Nov. 6. Huang, a seasoned biotech analyst, was most recently head of biotech equity research at BofA Securities, the investment banking arm of Bank of America. As for Zhang’s chair of board duty, Legend has named its board member and Genscript’s chief operating officer, Ye “Sally” Wang, as chairwoman. In response to a recent Fierce Pharma request for an update on Zhang’s status, a Legend spokesperson referred to the original announcement in September.
Other than cilta-cel, Legend’s clinical CAR-T pipeline includes a CD19xCD22 bispecific for diffuse large B cell lymphoma, a CD33xCLL-1 bispecific for acute myeloid leukemia, a candidate targeting claudin 18.2, and an off-the-shelf CD20 therapy.