Biotech Strategy Blog

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

Posts from the ‘Lymphomas’ category

Aloha! It will soon be time to pack your Hawaiian shirts for the forthcoming BMT Tandem Meeting in Hawaii (Twitter #BMTTandem16 – what a long hashtag!!)

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Commonly known as “Tandem,” it’s the combined annual meetings of the Center for International Blood & Marrow Transplant Research (CIBMTR) and the American Society for Blood and Marrow Transplantation (ASBMT).

Hawaii is great location for a meeting in February, and one that I’m sure will generate a lot of envy for those who can’t attend and are stuck in the winter cold and chill. Who said we don’t go the “extra mile” for BSB subs?

One of the presentations I’m looking forward to hearing at Tandem is by Ann Leen, PhD, who is an Associate Professor at Baylor College of Medicine.

Dr Leen will be talking about “Immunotherapy for Lymphoma using T cells Targeting Multiple Tumor-Associated Antigens.

At last December’s ASH annual meeting, Dr Leen presented preliminary data with this novel approach in patients with Hodgkin’s Lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). After her ASH presentation, she kindly spoke to BSB.

This post is part of our post-meeting ASH15 coverage, and our ongoing coverage of some of the exciting developments in immuno-oncology.  In case you missed it, do check out the ASH interview with Seattle Genetics CEO Clay Siegall, PhD.

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SGEN Booth ASH15

Seattle Genetics ASH 2015 Exhibit – photo with permission

San Francisco – Seattle Genetics are presenting later today at the JP Morgan Healthcare conference (2.30pm PST) and we’ll be covering this as part of our daily rolling blog.

As blog subscribers already know, one of the presentations that caught our attention at ASH 2015 was the updated phase 1 data for Seattle Genetics latest ADC, denintuzumab mafodotin (SGN-CD19A) in B-cell malignancies, including diffuse large B-Cell lymphoma (DLBCL).

Unlike with brentuximab vedotin, where one of the main side effects seen is peripheral neuropathy, with 19A, as it’s commonly known, there is ocular toxicity. Will this toxicity bring the house of cards down for Seattle Genetics?

I spoke to President and CEO Clay Siegall, PhD about this, the company’s corporate strategy moving forwards in 2016 and how checkpoint inhibitors may impact classical Hodgkin’s Lymphoma (cHL).

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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.

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ASH 2014 cHL PembroOne of the hotly debated topics at the 2014 American Society of Hematology (ASH) annual meeting was the arrival of checkpoint data in classical Hodgkin’s lymphoma (cHL), with initial data presented on 20-30 patients with relapsed or refractory cHL who received either nivolumab (BMS) or pembrolizumab (Merck) in open label, single agent trials.

Updated phase I data is expected to be presented at the 2015 ASH annual meeting in Orlando (Dec 5-8) (Twitter #ASH15)

At the recent ESMO symposium on Immuno-Oncology in Lausanne (Twitter #Immuno15) – great hashtag, there was an excellent overview of checkpoint blockade in lymphomas. What did this tell us about progress in this disease and where are things going?

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The ESMO IO meeting set the scene for what we can expect at ASH this year?

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Dr Holbrook Kohrt StanfordHolbrook Kohrt MD PhD (pictured right) is a Stanford medical oncologist and clinical researcher who is leading the way in cancer immunotherapy combination strategies targeting CD137 (4-1BB).

He’s a speaker I greatly enjoy listening to at meetings. Earlier this year at The American Association of Immunologists (AAI) annual meeting (Immunology 2015) in New Orleans, he gave a noteworthy presentation on combination monoclonal antibody therapy.

The potential of a combination of an anti-CD137 monoclonal antibody such as urelumab plus an anti-CD20 such as rituximab, was one that he appeared to be particularly excited about.

Dr Kohrt kindly spoke with BSB and shared his thoughts on the potential of immune modulators, which instead of acting as inhibitors to “release the brake,” like checkpoint inhibitors, act as agonists to “step on the gas” and rev up the immune system. This is a concept that many Pharma companies are currently looking to explore for new drug development opportunities, for example:

Roche ESMO Media Briefing Immunotherapy Approach

Source: Roche Media Briefing at ESMO 2014 in Madrid

When it comes to combination strategies, the big unanswered questions are which ones will produce big gains in response rates and survival outcomes, and which ones will be duds?  

After all, much like targeted therapies, not all targets will be relevant in all tumour types – it will depend on the underlying immune system.

In New Orleans, Dr Kohrt talked about the potential advantages and concerns around combination strategies and why he’s particularly interested in CD137 as a novel target for immunotherapy.

In-Memorium Holbrook Kohrt 

It is with great sadness that we must report that Holbrook Kohrt is no longer with us. He died, aged 38, on February 24, 2016.

 

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Much has been written about the success of checkpoint blockade in solid tumours over the last couple of years with the advent of anti-CTLA4 therapy (ipilimumab/Yervoy) for metastatic melanoma followed by the more recent approval of the anti-PD-1 antibodies in advanced melanoma (pembrolizumab/Keytruda and nivolumab/Opdivo) and lung cancer (nivolumab).

What about hematologic malignancies though?

At the recent American Society of Hematology (ASH) conference, we heard about the first clinical data for anti-PD1 antibodies in patients with refractory classic Hodgkins Lymphomas (cHL) and saw some impressive results. Interestingly, though, the early preclinical work was conducted in mice looking at CTLA4 blockade in a variety of tumours, both solid and liquid.

YervoyIs there a rationale for targeting CTLA4 in leukemias, lymphomas and even myeloma?  New data presented at a medical meeting in patients with heavily pre-treated and relapsed disease post stem cell transplantation suggests that this might be feasible.

Check out to today’s article to learn more about this clinical opportunity in more detail – you can log in or subscribe in the box below.

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. 

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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’s time to answer some more subscriber questions. Several readers wrote in and asked about the anti-PD1 checkpoint data that was presented at the recent American Society of Hematology (ASH) meeting in classic Hodgkin’s lymphoma (cHL):

What did we think of it?

Well, for starters it was one of our highlights of the ASH 2014 conference (see quick write-up, open access), with an impressive 87% response rate for nivolumab in refractory cHL. Many of these patients had failed both autologous stem cell transplant and brentuximab (Adcetris), for which FDA granted breakthrough therapy designation.

ASH14 CHECKPOINTSOverall, I agreed with Ron Levy (Stanford) when he noted in the packed Special Session on Checkpoint inhibitors in Hematology that there were only 4 or 5 abstracts to actually discuss (he didn’t spend much time on the preliminary data) and that the results are still very early without seeing how good the durability will be.

As he observed in the session, which was standing room only, figuring out how best to integrate these new agents into clinical practice with other successful approaches will be most interesting.

That said, there are some new data that have emerged since ASH that are worthy of discussion in terms of potential future directions and how they could impact the checkpoint landscape in both hematologic malignancies and even solid tumours.

This is part of our ongoing immuno-oncology series on how we can manipulate T cells in creative ways to kill the cancer cells.  The findings discussed in this article are completely new and have not been discussed here before.

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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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PLA General HospitalThe announcement earlier this week that Cellular Biomedicine Group (NASDAQ: CBMG) has acquired rights to the Chimeric Antigen Receptor T cell (CAR-T) therapy of the PLA General Hospital in Beijing (pictured right) should come as no surprise to industry watchers. (Link to Press Release).

The share price in $CBMG has risen from $16.31 on February 4 to $23.60 as of close of business on Feb 10, 2015 in what looks like a poorly kept secret!  It looks like most of the rise in share price took place immediately prior to the company’s formal Feb 9, 2015 announcement of the Chinese deal.

CBMG Share Price

 

Those following the cancer immunotherapy space have known for some time that several Chinese groups are working on CAR-T cell therapies that could be a threat if licensed or acquired.

Given the significant investor interest in this space, which is almost bordering on “tulip mania,” it’s entirely foreseeable that companies looking to share in this opportunity would go looking towards China.

One investor on Twitter in response to this news asked should Chinese data be trusted?

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