Biotech Strategy Blog

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

Posts tagged ‘CD19 CAR-T Cell Therapy’

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.

To learn more, subscribers can log-in or you can sign up in the blue box below.

Aggressive lymphoma… the very phrase is enough to send chills down your spine!

ASH Annual MeetingIn the past, much of the focus at previous American Society of Hematology (ASH) meetings in this area has focused on the myriad of chemotherapy regimens and dose/schedule optimisations that followed in trying to boost patient outcomes.

This year, I’m pleased to say that things have quite a different flavour with numerous new therapeutics and promising combinations in development.

Some of these are inevitably hypothesis testing, while others will be up-levelling to large randomised controlled multi-centre trials.

As part of our ongoing preview series, we take a look at the different categories to watch out for beyond chemotherapy.  These include monoclonal antibodies, antibody drug conjugates, targeted therapies and yes, even immunotherapies.

To learn more, subscribers can log-in or you can sign up in the box below to read our latest in-depth article… 

Juno Therapeutics LogoThis morning we heard that Juno Therapeutics have registered their plans with the SEC for an Initial Public Offering (IPO), highlighting the desire of the VC investors to generate a fast turnaround on their money before a multi-center trial of their CAR-T cell therapy has even started!

One of the challenges with CAR-T cell therapy is despite some stunning results, particularly in pediatric ALL, it remains an experimental one with toxicities that have to been managed. Adult patients, who are extremely sick, have died on trials. If I was at the end of the line faced with certain death, I’d probably roll the dice and take an experimental therapy, but CAR-T cell therapy does have challenges that need to be addressed.

Indeed at the Society for Immunotherapy of Cancer (SITC) meeting last week, one of the Hot Topic sessions that took place after the conference formally ended was in managing the toxicities associated with chimeric antigen receptor T cell (CAR-T) therapy.

Of particular concern for all CAR-T cell therapies in development is severe cytokine release syndrome (sCRS), which requires treatment in hospital intensive care.

Cytokine release syndrome (CRS) involves fevers, hypotension, hypoxia and even neurological toxicities. It’s been known for some time to be a challenging side effect of CAR-T therapy. We first wrote about it at ASH 2012.

As Novartis, Juno and Kite all look towards multi-center registration trials, the identification of patients at risk of severe CRS (sCRS) and the management of this in very sick, often end stage patients remains a real challenge, especially given that we don’t fully know what causes it to occur in some patients, but not others. Patient deaths due to sCRS are not good news on any clinical trial, and even less so when it’s a novel therapy in development.

TWashington DC in Fallhis week sees the start of the 2014 annual meeting of the Society for Immunotherapy of Cancer (SITC) at National Harbor, MD.

Given the rapid progress that is taking place in the field of cancer immunotherapy, we’re excited to be flying up to DC to attend the meeting for the first time as part of our conference coverage.

SITC 2014 ProgramMany of the leading translational scientists in immuno-oncology will be at SITC to discuss the current landscape, challenges and opportunities.

For all the promising results we’ve seen so far, harnessing the body’s immune system to fight cancer is very much a work a progress.

Don’t expect much from SITC on social media, most of the data is likely to be unpublished, which is why you have to go to meetings like SITC, ARVO and AACR in person. An important part of attending is the in-person conversations and connections that take place.

SITC 2014 Conference AppYou can download the preliminary program on the SITC 2014 Annual meeting website. There’s also an iphone/android app for those attending.

Conference Highlights: 

  • Addresses by the 2014 Richard V. Smalley, MD Memorial Award recipient, Giorgio Trinchieri, MD – National Cancer Institute and the Annual Meeting keynote speaker, Olivera J. Finn, PhD – University of Pittsburgh
  • News on important initiatives and updates in cancer immunotherapy by key stakeholders in the field
  • Workshop on Combination Immunotherapy: Where Do We Go From Here?
  • Primer on Tumor Immunology and Cancer Immunotherapy™
  • Hot Topic Symposia on Managing Engineered T-Cell Toxicities & Accelerating Tumor Immunity with Agonist Antibodies.

If you haven’t already seen it, this educational video from Roche/Genentech, narrated by Dan Chen MD PhD (Cancer Immunotherapy Franchise Head) is not only educational in discussing the mechanism of action of their anti-PDL1 monoclonal antibody, MPDL3280A, but is highly fun and entertaining to watch. Enjoy!

Sally interviewed Dr Chen at ASCO this year for a blog post from the meeting on “Making a difference in advanced bladder cancer.”

Subscribers, whose support helped fund us to go to SITC for the first time, can login below to read more about the 2014 annual meeting at National Harbor, MD or alternatively, you can purchase access via Tinypass by clicking on the blue icon below.

At ASCO 2014, one of the posters that attracted a lot of attention was the one from Kite Pharma ($KITE) on their rapid cell expansion (RACE) technology for the production of engineered autologous T cell therapy.

Dr Renier Brentjens at 2012 Chemotherapy Foundation Symposium

As regular blog readers will know, we’ve been following the development of CD19-targeted T cells for the treatment of B cell malignancies such as CLL, ALL and aggressive NHL for some time.

Back in Autumn 2012, at the Chemotherapy Foundation Symposium (CFS) in NYC, more commonly known as the “Greenspan” meeting after the late Dr Ezra Greenspan, we heard presentations on early CAR-T cell data from Dr Renier Brentjens (pictured right) of Memorial-Sloan Kettering Cancer Center (MSKCC) and Dr Michael Kalos from the University of Pennsylvania (Penn).

At ASH 2012, we wrote about the data presented by Dr Carl June in the Ernest Beutler Prize Lecture. Dr Blazar, who jointly received the award, gave this quote from Dr Beutler, which is a reminder of why basic science is worthy of funding, and how important it is to innovation:

“The tendency to merely elaborate on what many others are doing arises, at least in part, from the almost universal misconception that our understanding of nature is profound, that most or all of the basic concepts have already been discovered, and that success in science consists of filling in the blanks with large teams of collaborators.”

What started off as pure academic research, has within a short period of time, become a hot (if not the hottest) area of immunotherapy drug development as inspired by the potential of early data, companies and investors pour money into commercializing CAR-T cell therapy.

Novartis had obtained the exclusive rights to Penn’s CTL019 CAR-T cell therapy in August 2012 at what now seems a bargain price.

Juno Therapeutics was subsequently created with $176M in Series A private equity funding at the end of 2013 to commercialize the CAR-T cell research of Memorial Sloan Kettering in New York and Seattle’s Fred Hutchinson Cancer Research Center.

Last week brought further development with an Initial Public Offering (IPO) from Kite Pharma who have a collaboration with the National Cancer Institute (NCI). Kite said they expected to raise $106M at a share price of $17, which was at the high end of the range. The shares soared 70% in initial trading, and closed at $29 on Friday.

To throw more fuel into the competitive fire, Pfizer have announced the signing of an agreement with French company, Cellectis, to collaborate on the development of their CAR-T cell technology.

In this first of a series of blog posts on gems from the ASCO poster hall, we take a look at the data presented by Kite Pharma and some of the challenges and opportunities the company faces.

Please note this post offers no investment advice and makes no recommendation on whether you should buy or sell shares in $KITE.

Subscribers can login below to read more or you can purchase access by clicking on the blue icon below:

error: Content is protected !!