Welcome to your weekly roundup of EP Vantage’s snippets – short takes on smaller news items.
This week, September 19-23, 2016, we had thoughts on the following: Persongen beats Nantkwest (NASDAQ:NK) to the clinic; Chinese group tries to drive two CARs; second me-too success has Teva (NYSE:TEVA) looking backwards as well as forwards; J&J's (NYSE:JNJ) PD-1 asset comes out of stealth mode; the end of vepoloxamer surely means the end for Mast Therapeutics; J&J CD123 project suspended – what else is in the pipeline?
These snippets were previously published daily via twitter.
Persongen beats Nantkwest to the clinic
September 23, 2016
Back in March Nantkwest, the cell therapy company founded by the billionaire Patrick Soon-Shiong, was still aiming to start clinical trials this year with CD19.taNK, its CD19-directed CAR-NK project. However, the Chinese group Persongen Biotherapeutics has beaten it to the punch, according to a filing on Clinicaltrials.gov. The study, which started this month, uses a construct that Persongen calls PCAR-119, based on the NK-92 cell line, as a bridge to stem cell transplantation in 10 leukaemia and lymphoma patients; NK-92 is a continuously growing line of natural killer (NK) cells identified in 1992, which Nantkwest plans to use for its CAR-NK constructs as well as other uses. However, while Nantkwest claims to have exclusive rights to NK-92, it is appealing against the USPTO’s rejection of a key patent, and Persongen’s study suggests that ownership is far from clear. NK cells can be used allogeneically, though they are more difficult to handle than T lymphocytes. Nantkwest made no mention of CD19.taNK in its last quarterly filing, but still plans to be in the clinic with another CAR-NK asset, this one targeting Her2.
Chinese group tries to drive two CARs
September 23, 2016
The problem of leukemia patients relapsing after CD19-directed CAR-T therapy is well documented, prompting groups like Juno and Novartis to investigate post-relapse retreatment with a CAR targeting a separate antigen, CD22. Now a group at Xuzhou Medical University in China claims to be the first ever to administer both types of CAR simultaneously, according to a 20-patient study filed on Clinicaltrials.gov. The group argues that treatment with sequential infusion might open up a window for tumor recurrence, which a dual approach could avoid. Of course, two separate vector transfections could double the already high cost of the procedure. A related approach – a bispecific CD19/CD22 CAR – is being pursued preclinically by the NCI, but while only involving one transfection this introduces possible geometric difficulties and problems with uneven activation of the cells. The Chinese study will test equal doses of the two CARs, but clearly could allow for dosing flexibility in future; the trial starts this month.
Second me-too success has Teva looking backwards as well as forwards
September 23, 2016
Teva’s second phase III tardive dyskinesia success with its VMAT2 inhibitor Austedo has drawn obvious comparisons with its future rival Neurocrine, but generic forms of Valeant (VRX)/Lundbeck’s (OTCPK:HLUYY) Xenazine must also be borne in mind. This is because both Austedo and Neurocrine’s Ingrezza are me-too versions of Xenazine – the former a deuterated form of Xenazine’s active ingredient and the latter a metabolite. Austedo added to its earlier success in a dose-titration trial with a positive readout in AIM-TD, a study in which fixed 12mg, 24mg and 36mg doses were tested, and the highest two beat placebo with p<0.05. The data look on a par with Ingrezza’s, though Evercore ISI’s Umer Raffat points out that baseline values might not be comparable, and Neurocrine’s results might not reflect an intent-to-treat population. Xenazine is a benchmark owing to pricing considerations – Leerink analysts reckon on Austedo costing just $45,000 per patient per year versus Xenazine’s $83,000 – and Austedo and Ingrezza’s relative safety could be key. Teva aims to file this year, while Neurocrine has already done so.
J&J's PD-1 asset comes out of stealth mode
September 22, 2016
There was no fanfare or preamble; instead J&J quietly launched its first effort in the PD-1 space on Monday with a filing on Clinicaltrials.gov. The project, which so far only has a research code, JNJ-63723283, joins an increasingly crowded field that already has three other early-stage anti-PD-1 assets. J&J’s trial will be an open-label phase I/II study to determine the pharmacokinetic, pharmacodynamic and clinical activity of JNJ-63723283 in patients with advanced cancers. The two-part 169-patient study is due to start enrollment this month, and will look at a selected number of solid tumors including non-small-cell lung cancer, melanoma, renal, bladder and gastric cancers, with an estimated completion in April 2019. But with other companies significantly ahead, and the lung and melanoma spaces awash with checkpoint inhibitors, the success of J&J’s venture could hinge on its efficacy in more neglected tumor types.
The end of vepoloxamer surely means the end for Mast Therapeutics
September 21, 2016
After months of fruitless searching for an efficacy signal in the pivotal Epic trial, Mast Therapeutics has finally admitted that vepoloxamer is over. And despite an immediate move into survival mode the company’s future looks bleak. Shares fell 79% in early trade today to value the company at $27m; it ended the second-quarter with $35m in the bank, and a looming $10m debt repayment darkens the picture further. Mast owes the debt-financing firm Hercules Capital $15m, and the failure of Epic makes the principal amount due by October 14. The failure of the study is incontrovertible: vepoloxamer did not significantly shorten the vaso-occlusive crises suffered by sickle cell anaemia patients (p=0.09), while two secondary endpoints were also missed. This marks the third phase III calamity for the company in the past nine years – it has come back before, but this time surely resurrection is impossible.
J&J CD123 project suspended – what else is in the pipeline?
September 19, 2016
Scratch one from the pipeline of antibodies targeting CD123 in haematological cancer. Recruitment in the phase I dose-escalation trial of the Johnson & Johnson/Genmab project JNJ-63709178 has been suspended because of a serious adverse event. The bispecific antibody was being tested in patients with acute myeloid leukaemia, with the hope of, in addition to proving safety, showing signs of depletion of cells expressing CD123, which is expressed on cells of the myeloid lineage. JNJ-63709178 binds with both CD123 and CD3, a protein found in cytotoxic T cells, with the goal of crosslinking the two and enabling tumor cell destruction. Should the current suspension become permanent, the clinical-stage CD123 pipeline will comprise such assets as XmAb14045 and MGD006 having similar mechanisms to JNJ-63709178, and SL-401 being a cytokine-toxin conjugate.