Mustang Bio’s first-of-a-kind CAR-T starts trials

US biotech Mustang Bio says that an investigator-led trial of its CAR-T therapy for multiple myeloma – the first to target CS1 protein – has started recruiting patients.

The multiple myeloma pipeline is filled with CAR-T therapies but most are targeting BCMA, including Celgene’s bb2121 which is considered the pacesetter in the race for approval in the category with an FDA verdict due later this year.

Mustang reckons that by targeting CS1 – also known as CD319, CRACC and SLAMF7 – its MB-104 CAR-T will be differentiated from the BCMA pack and could carve out a lucrative niche in the large and growing multiple myeloma market.

CS1 is expressed by cancer cells in nearly all multiple myeloma patients, and also has low expression in normal tissues, preventing those cells from being severely damaged during treatment.

The trial will be carried out at City of Hope cancer treatment and research centre in Southern California, which is fast becoming one of the premier facilities in the US for cell therapies. It will enrol heavily pre-treated myeloma patients who have received at least three prior treatment options and test positive for the CS1 antigen.

“Multiple myeloma accounts for 10% of all blood and bone marrow cancers,” said Xiuli Wang, a City of Hope research professor who has been involved in testing MB-104 in preclinical and translational research.

“CS1 is a very promising target for multiple myeloma patients who currently have few viable treatment options," she added.

There is a precedent for the therapy as CS1 is targeted by Bristol-Myers Squibb and AbbVie’s multiple myeloma antibody Empliciti (elotuzumab), which has been tipped to become a blockbuster product but has been sluggish in its sales growth since reaching the market in 2015. Last year BMS, which books sales for the product, said it made $247 million in Empliciti revenues.

Mustang also announced this week that it had raised $32 million in a public offering that will help it fund its CAR-Ts for blood cancer, solid tumours and rare genetic diseases.

Along with MB-104. Mustang’s cancer-targeted CAR-T’s include MB-102, a CD123-targeting therapy for acute myelogenous leukaemia that is also partnered with City of Hope and due to start trials shortly, and MB-106, a CD20-targeted therapy partnered with Fred Hutchinson Cancer Center and heading towards trials in non-Hodgkin lymphoma and chronic lymphocytic leukaemia.

Its most advanced project is MB-107, a gene therapy licensed from St Jude Children’s Research Hospital for X-linked severe combined immunodeficiency (X-SCID), also called ‘bubble boy’ syndrome, that is in a phase 1/2 trial. Data from the trial were published in the New England Journal of Medicine last month.