ASH – Second chances for Bluebird and Novimmune

Bluebird Biotech earned a dubious distinction as the first big loser of this year’s ASH conference, but it now has a chance to salvage some pride. This is courtesy of an ASH late-breaking study conducted by the NIH that could have a read-across to its own lead CAR-T project.

This was not the only second chance offered up by yesterday’s unveiling of the ASH late-breaking abstracts. A low-key private Swiss biotech, Novimmune, could be close to a therapy for haemophagocytic lymphohistiocytosis, a rare blood disorder, with a project that Merck KGaA had earlier ditched.

Bluebird stock had lost 22% as investors adjusted to more realistic expectations on publication of its beta-thalassaemia gene therapy abstract at ASH earlier this month (ASH preview – Cellectis steals the limelight, November 6, 2015). Yesterday the shares crept up 4%.

The NIH work in question concerns a first-in-human study of a CAR-T construct against B-cell maturation antigen (BCMA), a protein expressed by plasma cells. These cells – effectively antibody-producing B-cells – are malignant in multiple myeloma, and thus this was the setting in which the NIH project was tested.

The abstract, which will likely be updated at ASH, details 11 of the first 12 patients treated, with efficacy comprising one complete and two partial remissions, and seven stable diseases, which the researchers call a demonstration of strong anti-myeloma activity; the patients had had a median of seven prior lines of therapy.

The data provide an important guide for Bluebird since a BCMA project, bb2121, is now the key focus of its own CAR-T collaboration with Celgene. The deal had previously been broad, based around work at Baylor College of Medicine, among others, but Celgene took a step back earlier this year.

Of course, a key aspect to watch will be safety, especially since BCMA is present on normal as well as malignant plasma cells. The ASH abstract mentions cytokine release syndrome – a serious side effect associated with strong response to cell therapy – in two patients on the highest dose of the CAR-T cells.

Another interesting aspect is that the NIH has a co-operative R&D agreement (CRADA) with Kite Pharma, but Kite has not spoken of this including an anti-BCMA CAR-T project. The abstract’s presenting author, the NIH’s Dr James Kochenderfer, has a separate CRADA with Bluebird, and will be a primary investigator in bb2121's phase I study, starting next year.

Rare disease

Meanwhile, Novimmune will be celebrating getting NI-0501, an anti-interferon-gamma MAb, into an ASH late-breaker detailing an open-label trial in 13 children with primary haemophagocytic lymphohistiocytosis (HLH).

This rare autosomal recessive disorder is characterised by excessive T lymphocyte and macrophage activation, and is currently controlled with steroids, chemotherapy and intravenous immunoglobulin. Researchers write in the ASH abstract that high production of interferon-gamma is thought to be a critical disease driver, hence the rationale behind NI-0501.

The pilot trial showed nine of the 13 children achieving a “satisfactory” response in terms of parameters of disease activity, though two of the other four died of HLH within eight weeks. The researchers highlight NI-0501’s safety profile, reporting none of the toxicities reported with chemo, for instance.

NI-0501 looks like a promising way of getting patients into a strong enough condition to accept a stem cell transplant, with seven of the children proceeding to this, and transplant planned in a further two on identification of an appropriate donor.

Rare diseases are a growing focus for many companies, given the possibility of orphan pricing and the relatively low regulatory hurdles involved. Novimmune has made quiet progress over the past 17 years, though it has not had a rare disease focus.

Its lead asset, foralumab, is partnered with the private UK group Tiziana life Sciences for Crohn’s disease. NI-0501 had in 2005 been licensed to Merck KGaA for lupus and Crohn’s, but Merck handed it back six years ago.

Novimmune closed a CHF60m ($59m) financing in February 2014. The ASH data could open up some new possibilities.

This story has been amended to add information about the CRADA between the NIH/Dr Kochenderfer and Bluebird. 

To contact the writer of this story email Jacob Plieth in London at [email protected]. For live updates from the ASH meeting in Orlando, on December 4-8, follow @JacobPlieth on Twitter.