Biotech Strategy Blog

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

Posts from the ‘CAR-T’ category

Juno Therapeutics LogoThis is an important and necessary follow-up to the ongoing Juno JCAR015 story in July after three patients had died due to complications associated with cerebral oedema. At that time, the company attributed the deaths to the inclusion of fludarabine in the lymphodepletion given prior to CAR T cell therapy infusion, leading to severe neurotoxicity, and clinical hold was lifted by FDA after the protocol was subsequently amended.

This morning came the dramatic announcement that following the protocol amendment, Juno has voluntarily placed the ROCKET trial on clinical hold again following another two deaths from cerebral oedema.

What gives and what are the consequences here?

We take a joint look at some of the issues that arise from this situation in terms of the CAR T cell therapy market and also pen thoughts from the analyst call this morning.

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It was only five years ago that the number of abstracts on CAR T cell therapies at the American Society of Hematology (ASH) ran to a dozen or less. Fast forward to 2016 and we now have tens of them, almost too many to count, let along review quickly and easily.

ash-annual-meeting

A scene from ASH 2015…

To give you an idea of the staggering speed of progress, in 2010 it took me less than half an hour to search and read all the CAR T cell abstracts, now it takes nearly a whole day to peruse and review them carefully.

We can’t resist a challenge…

As usual, we will write in more depth from the meeting as the data emerges in real time since many of the abstracts are often placeholders with updated information provided at the conference itself.

For now, here we provide an in-depth preview of the CAR T cell landscape in terms of the players, the products, new scientific research, biomarkers, emerging trends and more in a handy What to Watch For (W2W4) guide on key areas to expect at ASH to enable better enjoyment and awareness as the data rolls out next month.

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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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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!

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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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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Some people may think that if you just give a whole boat load of engineered T cells, and in particular, those modified with a Chimeric Antigen Receptor (CAR), that responders are “cured.”

While some recipients of engineered T cells can have long-term, durable remissions, others may initially respond, only to subsequently relapse.

Resistance to CAR T cell therapy can and does occur.

In this post, we talked with a leading expert about the latest research on how resistance to cell therapy develops, and the potential strategies to overcome it.

CAR T cell therapy is exciting, but remains an emerging field with multiple ways in which the competitive landscape may be shaped moving forwards.

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That’s the $64K question we all want to know, and what’s more is gene editing necessary when it comes to creating an “off-the-shelf” T cell therapy, which instead of modifying a patient’s own T cells (autologous), uses cells from a healthy donor (allogeneic)?

We were really curious too, and sought out one of the world’s leading experts for their opinion on this very issue.

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The 2015 Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT 2015) was held in Istanbul from March 22-25, where it offered a European perspective on some of the latest developments in cancer immunotherapy. 

EBMT 2015 banner

We’ve heard a lot in the United States about the early CAR T cell therapy clinical trial results from institutions such as UPenn, CHOP, MSKCC, Fred Hutchinson, Seattle Children’s, the NCI, and MD Anderson to name but a few, so it was good to see a leading a European center join the club: University College London (UCL).

While completing a Masters degree in Human and Applied Physiology at King’s College London, I spent several weeks training at UCL and particularly enjoyed the intercollegiality of the University of London.

At EBMT15, Dr Sara Ghorashian Clinical Training Fellow at the Insitute of Child Health at UCL, presented data on a phase 1 trial of Epstein Barr virus (EBV) specific T cells transduced with a first generation CD19 Chimeric Antigen Receptor (CAR). The trial data was first reported by Dr Ghorashian (pictured below) in an oral presentation at #ASH14 (Abstract 383).

Dr Sara Ghorashian ASH 2014

Dr Ghorashian stated at EBMT that UCL have several CAR T cell therapy trials planned.

autolus-logoReaders will be aware that earlier this year that UCL spun-off a series A funded company, Autolus, to commercialize their CAR T cell therapy research.

Although £30m from Syncona (a subsidiary of the Wellcome Trust) is not a lot of money by US investment standards, UCL is nonetheless a European center to watch if you have an interest in the CAR-T competitive landscape.

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It remains exciting times in cancer immunotherapy with breakthrough new cell therapies and checkpoint inhibitors that enhance the effectiveness of T cells.

Cellectis LogoLast Friday, Paris based Cellectis filed their IPO registration statement with the Securities and Exchange Commission (Link to F-1).

They plan to raise $115M through an offering of American Depository Shares. You can read more about their allogeneic Chimeric Antigen Receptor (CAR) T cell approach in the two interviews we did with senior management last year.

Here’s an excerpt of the interview Cellectis CEO André Choulika, PhD gave Biotech Strategy Blog last year – it was the No1 post in 2014: Can Cellectis Revolutionize CAR-T cell Immunotherapy?

As multiple companies seek to move CAR-T cell therapies forward in clinical trials, what will be interesting to see is how this novel treatment fits in with existing therapies such as bone marrow transplants. Will it replace them, or be a bridge to a transplant that enables relapsed or refractory patients to have a second chance?

In addition, where are the potential opportunities beyond B-cell malignancies such as acute lymphoid leukemia (ALL) where there’s been dramatic success, particularly in children?

Dr Krishna KomanduriLast week Biotech Strategy Blog had the privilege to interview Dr Krishna Komanduri who is Director of the Adult Stem Cell Transplant Program at the University of Miami Sylvester Cancer Center and holds the Kalish Family Chair in Stem Cell Transplantation.

A physician scientist, he exudes a sense of calm professionalism – I am sure this must reassure many of his patients. Having a bone marrow transplant has been likened to jumping off a cliff in terms of what it does to one’s immune system.

In the last 2-3 years, he has dramatically increased the number of transplants at the University of Miami Sylvester Cancer Center.

Dr Komanduri (@DrKomanduri) was co-chair of the 2015 BMT Tandem meeting that took place earlier this month in San Diego. It’s the combined annual meeting of the American Society of Blood and Marrow Transplantation (ASMBT) and the Center for International Blood and Marrow Transplant Research (CIBMTR).

In a half hour interview he shared his thoughts on what was exciting at Tandem, where the field is going and some of the best abstracts at the meeting which included data on CAR-T cell therapy, GVHD and gene therapy.

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