Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts from the ‘Hematology’ category

Cellular immunotherapy with Natural Killer (NK) cells is emerging as a potentially effective treatment option for older patients (more than 60 years of age) with Acute Myeloid Leukemia (AML).

AML remains a disease with high unmet medical need, particular for those patients who relapse and are ineligible for a stem cell transplant (SCT).

There’s considerable buzz around adoptive cellular therapy and, in particular, chimeric antigen receptor modified T cells (CAR T cells). It is important, however, to note that there are other approaches worthy of consideration. See post: Could a Novel Cell Therapy replace CAR T cell therapy?

Cancer immunotherapy targeting NK cells has already shown some early promising results in AML. We await the read out of the EFFIKIR trial data for lirilumab (Innate Pharma/BMS), an anti KIR (killer inhibitory receptor monoclonal antibody. See post: Innate Pharma at an Inflexion Point, an interview with Hervé Brailly.

357-cover-sourceRizwan Romee, Maximilian Rosario, Melissa Berrien-Elliott and colleagues at the Washington University School of Medicine in St Louis (@WUSTLmed) recently published the results of a clinical trial with a novel NK cell therapy: “Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia.”

The paper was published on 21 September, 2016 in Science Translational Medicine (link).

Melissa Berrien-Elliott, PhD. Photo Credit: Fehniger Laboratory, Washington University

To better understand the trial results and what they tell us about NK cell therapy in AML, BSB spoke with one of the joint first authors, Melissa Berrien-Elliot, PhD (pictured right) and senior author, Todd A Fehniger MD PhD, Associate Professor of Medicine at Washington University.

This post is part of our series on the innate immune system.

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No CyclingLate this afternoon, Juno Therapeutics ($JUNO) announced (link to press release) that the FDA had put a clinical hold on enrollment into a phase 2 trial of their JCAR015 construct in relapsed refractory acute lymphoblastic leukaemia (ALL) in adults in the ROCKET Trial: NCT02535364.

The decision by the FDA was as a result of three recent patient deaths reported to be due to neurotoxicity. In after-hours trading the stock dropped 30% from a market close of $40.82, reaching an after hours low at time of writing of $26.66 at 4.43pm ET.

In this post we look at what happened, the possible reasons behind it, and what it may mean for other CAR T companies. A leading CAR-T cell expert also provided BSB with some commentary after the news broke.

Good News: Post now updated following FDA lifting hold on ROCKET trial.

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This morning, like many folks, I woke up to the latest immuno-oncology news on the bispecific front that Xencor, a Los Angeles based biotech, announced their latest collaboration, this time with Novartis.

Over the last few years, we have seen a surfeit of bispecifics emerge that are focused on stimulating the immune system, particularly with regard to T cells and natural killer (NK) cells, as well as antigen targets on the surface of tumours. The first one approved was Amgen’s blinatumomab (Blincyto), a CD19 targeted bispecific for the treatment of acute lymphoblastic leukemia (ALL), which we have written extensively about.

Xencor logoThe Xencor/Novartis deal has a number of interesting implications that are well worth exploring in more depth that go far beyond the information provided in the press release.

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I was thinking that the reader mailbag questions this week would be full of straightforward easy to answer clinical questions, after all, they usually are post ASH and ASCO… but not this year!

T-cells attacking a cancer cell. Digital illustration.

T-cells attacking a cancer cell. Digital illustration.

Instead, there is a huge wall of intense focus on CAR T cell therapies and the latest round of intriguing developments in this space.  While CARs have received much attention, TCR cell products have largely flown under the radar to date, although that may change.

What’s particularly interesting is that these charges could potentially be transformative or absolute duds – it’s unlikely to be an indifferent middle ground here.

Here, we answer questions on the ever-increasingly complex science that is ongoing in the TCR and CAR T cell fields.

In the next mailbag, we will cover the clinical questions arising from data at ASCO, so if you have any queries on the data in Chicago, there’s still time to send them in before next Friday!

If you are interested in the new developments in the complex world of gene editing and how they may impact the ever-changing adoptive cell therapy space, then this article is for you.  Subscribers can log-in below or you can click the Blue Box to nab instant access!

Jounce Poster AACR 2016

The AACR Poster Halls get packed quickly!

It’s time to change direction and take a look at some of the Gems from the Poster Halls at the recent American Association for Cancer Research (AACR) meeting.

One particular abstract that looked interesting related to the Aduro compound, BION–1301, which is a monoclonal antibody targeting the B cell Maturation Antigen and its ligand, A Proliferation Inducing Ligand (BCMA-APRIL) in multiple myeloma.

Increasingly, there has been a lot of clinical interest in the BCMA target, but what about APRIL?

We spoke to one of the scientists involved in the research about this novel agent:

“It is very effective at abrogating the activity of APRIL and, in particular, in our models blocks the growth, survival, drug resistance, migration and adhesion of myeloma cells both in-vitro and in-vivo in our murine models. These models have been predictive for clinical activity of other novel targeted therapies including lenalidomide and bortezomib, and so we think targeting APRIL represents a very promising strategy.”

Sounds pretty good, right?

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Dr Michel Sadelain AACR 2016

Dr Michel Sadelain at AACR 2016

Dr Michel Sadelain, Director of Cell Engineering at Memorial Sloan Kettering Cancer Center in New York is a pioneer in the field of adoptive cell therapy.

Without his contribution, it is unlikely CAR T cell therapy would be where it is today.

He’s also President of the American Society of Gene and Cell Therapy (ASGCT), whose annual meeting is currently underway in Washington DC from May 4 to 7 (Twitter #ASGCT16).

Recently at the annual meeting of the American Association for Cancer Research (AACR), Dr Sadelain gave an outstanding presentation on turbo-charged CAR T cells, and shared some of his ideas on how to move the field forward.

In New Orleans, he also kindly spoke to BSB, and discussed how he thinks cell therapy researchers may obtain the “holy grail” of getting CAR T cell therapies to work effectively in solid tumors.

Dr Sadelin is someone who wants to break the immunology rules!

Not surprisingly, Dr Sadelain is optimistic and doesn’t share the view expressed by Dr Steven Rosenberg on CAR T cell therapies being limited to mostly hematologic malignancies when we interviewed him a year ago at last year’s ASGCT meeting.  There’s nothing like a friendly controversy to spice the field up!

If you haven’t already done so, do listen to Dr Rosenberg on Episode 5 of the Novel Targets Podcast (@TargetsPodcast).

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Koko Crater Botanical Garden

Hawaii, 2016

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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King Kamehameha Statue Honolulu HI

King Kamehameha Statue, Honolulu HI

Honolulu: we’re continuing our coverage of the 2016 BMT Tandem meeting with a thought leader interview about a novel cancer immunotherapy approach that we’re excited about.

The cancer cell therapy landscape is still vastly uncharted territory in many respects.

The first CD19 targeted CAR T cell therapies expected to reach the market in 2017 are unlikely to be best-in-class, which leaves the commercial door open for other approaches that may be better, cheaper or more accessible.

If you are in the CAR T cell therapy space, there are plenty of competitive threats on the horizon, and the novel approach discussed in this post is one of them!

We’d heard a little about it, but hadn’t explored the concept in any detail, so were delighted to talk with a leading expert at the BMT Tandem meeting in Honolulu.

Subscribers can login or you can purchase access to read more about a cell therapy that could offer the benefits of a CAR without the need for genetic modification.

Honolulu: Yesterday we learnt the sad news that Dr Holbrook Kohrt (pictured) had died.

Dr Holbrook Kohrt He was a Stanford hematologist/oncologist and rising star in the cancer immunotherapy field. Our thoughts go out to his family and friends.

I had the privilege to interview him last May at the Immunology 2015 meeting in New Orleans. His voice lives on in Episode 6 of the Novel Targets Podcast. One area of Dr Kohrt’s research was in combination immunotherapies, and how we can optimize efficacy, while avoiding significant immune adverse events.

So are checkpoints playing with fire when given in combination?

That was one of the provocative questions to come out of a scientific session entitled, “Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a platform for Novel Immunotherapies” at the BMT Tandem meeting in Hawaii last weekend. The session, chaired by Miguel-Angel Perales (@DrMiguelPerales) from Memorial Sloan Kettering Cancer Center, was both informative and interesting.

All the presentations were excellent, but one by Philippe Armand from the Dana-Farber Cancer Institute in Boston, “Checkpoint Blockade in SCT, Data & Hope, Promise & Peril” stood out for me. Dr Armand discussed checkpoint data pre and post stem cell transplantation and offered a perspective I had not heard before.

One of the provocative questions it raised was could checkpoints be playing with fire in some patients? Dr Armand kindly spoke with BSB after his talk.

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Honolulu: At the BMT Tandem meeting that ended yesterday in Hawaii, one of the hot topics was CAR T Cell Therapy. This should, perhaps, come as no surprise to readers given that bone marrow transplanters are not only the investigators doing the clinical trials, but will be the initial target market for this product.

Dr Micheal JensenOne of the pioneers in the development of adoptive cellular therapy is Michael Jensen (pictured) who is Director, Ben Towne Center for Childhood Cancer Research at Seattle Children’s Research Institute (SCRI) and the Sinegal Endowed Professor of Pediatrics at the University of Washington School of Medicine. Dr Jensen is also a scientific co-founder of Juno Therapeutics, Inc.

He’s been doing research in the field for over 20 years, and told me that not so long ago there would only be a handful of people in the room for a CAR T cell presentation!

In a plenary scientific session at the Tandem meeting, he presented to over 3,000 attendees on “CD19-Specific CAR T Cells as a Post-ALLO HSCT Relapse Salvage Therapy.”

After his presentation, he kindly spoke with BSB. This post describes some of the key take-homes from his talk.

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