It’s Day 7 of our 12 day Countdown to AACR 2016 in New Orleans. After exploring GITR and OX40, we’re now looking at another stimulatory target for cancer immunotherapy: CD40.
We’ve been writing about CD40 as a cancer immunotherapy target for some time. See posts: “CD40 as a Cancer Immunotherapy Target” and “Targeting CD40 in Cancer Immunotherapy.”
Anti-CD40 antibodies are agonists that act on stimulatory signalling receptors on T cells and antigen presenting cells (APCs). Targeting CD40 effectively acts to “put the foot on the gas” and may help generate a better immune response. This could be important in cancers that have fewer natural T cells present.
CD40 is an attractive target because it’s expressed in more than 50% of carcinomas and melanomas and almost all hematological B cell malignancies. Of particular interest is the potential to combine a CD40 agonist with a PD-1/PD-L1 checkpoint inhibitor.
Multiple companies have CD40 agonists in clinical development including Roche, Apexigen, Alligator Biosciences and Seattle Genetics. There are others coming too.
In this preview of AACR 2016, we’re looking at the CD40 landscape. New products and companies have entered the scene, so we’re highlighting them and some of the CD40 presentations to look out for at AACR 2016 (and why they matter).
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One of the most common questions we have received from subscribers in the last 6 months relates to Bellicum Pharmaceuticals (NASDAQ: BLCM) and the opportunity for their adjunct T Cell therapy in development for allogeneic hematopoietic stem cell transplantation (HSCT), BPX–501. This product is given after the transplant and uses genetically modified donor T cells incorporating a CaspaCIDe safety switch.
We first wrote an in-depth piece about Bellicum and BPX-501 back in January 2015 with an interview with their CEO and CMO for those interested in more background (Link).
At the recent 2016 BMT Tandem meeting in Hawaii, we had the opportunity to hear the latest data on trends in haplo-identical (Haplo) bone marrow transplants. This posts reviews some of the data presented and considers the implication of this on the market opportunity for Bellicum.
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ASH 2015 — taken before 7am!
Orlando – a presentation in the plenary session at #ASH15, the 2015 annual meeting of the American Society of Hematology, is the pinnacle of any doctor or researcher working in the hematology field.
Yesterday, we had the privilege to interview Dr Richard Stone (Dana-Farber Cancer Institute) ahead of his plenary presentation at ASH:
Abstract 6: The Multi-Kinase Inhibitor Midostaurin (M) Prolongs Survival Compared with Placebo (P) in Combination with Daunorubicin (D)/Cytarabine (C) Induction (ind), High-Dose C Consolidation (consol), and As Maintenance (maint) Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML) Patients (pts) Age 18-60 with FLT3 Mutations (muts): An International Prospective Randomized (rand) P-Controlled Double-Blind Trial (CALGB 10603/RATIFY [Alliance])
Anyone who has been to an ASH education session on AML knows how hard a nut it is to crack, so it’s wonderful to see some positive data, in what is commonly considered to be a “graveyard” disease.
The trial has taken a long time to come to fruition, so all credit to Dr Stone and colleagues. We’ll be writing up more about the data in our post meeting coverage. For additional background, you can also check out our FLT3 preview in AML, which details some of the history and context for this study. The data from the phase 3 study is likely to form the backbone of a registration filing for Novartis with this compound in the near future based on successfully meeting the trial endpoints.
We also kick off today’s highlights with quick reflections on some of the hot topics that emerged yesterday including Bluebird Bio’s lentiglobin, Bellicum’s pipeline and .
During the day, as the opportunity presents, we’ll also be providing commentary on sessions we attend.
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The immuno-oncology space continues to get both interesting and also very crowded with over 20 chimeric antigen receptor (CAR) T cell therapies now in development. Originally, the excitement began with the University of Pennsylvania’s dramatic announcement regarding the first two advanced CLL patients they successfully treated, leading to a collaboration with Novartis and spurring a new ‘arms race’ development in this niche.
While most of the CAR T cell therapy data since has largely focused on acute lymphoblastic leukemia (ALL) and to a lesser extent, non-Hodgkins lymphoma (NHL), many have been wondering what was happening on the CLL front? Has hope been abandoned there or will we see a renaissance occur? It is of particular relevance with the Abbvie/Genentech announcement that venetoclax has positive data in CLL patients who have the Del17p mutation and filing is likely here in this subset soon. Therapies such as ibrutinib and idelalisib are already approved in refractory CLL and may also have a future role to play here.
Do we need suicide switches for CAR T cell therapies such as Bellicum and Cellectis are developing or not?
Meanwhile, other hematologic malignancies are also being explored, including multiple myeloma. Why would a CD19 CAR work in a disease long considered to be CD19-negative in advanced, refractory disease?
Dr Carl June, U Penn
What about progress with solid tumours? Many commentators and investors have been highly sceptical of the chances of success here following the advent of positive checkpoint data beyond metastatic melanoma and early CAR data in mesothelin cancers.
To answer these questions and also get a flavour for where things are headed with CAR T cell therapies, we recently interviewed one of the leading experts in this field, Dr Carl June (U Penn).
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