Biotech Strategy Blog

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

Posts from the ‘CLL’ category

Dr David Porter, U Penn

Dr David Porter, U Penn

Honolulu: The BMT Tandem meeting kicked off yesterday with an excellent plenary session on “CAR T Cell Therapy: CD19 and Beyond.” The three presenters were:

  • David Porter (University of Pennsylvania) CAR T cells for Leukemia
  • Martin Pule (UCL) Building a CAR
  • Michael Jensen (Seattle Children’s) CD19-Specific CAR T Cells as a Post-Allo HSCT Relapse Salvage Therapy

Dr Porter (pictured) is Director of the Blood and Marrow Transplant Program at the University of Pennsylvania. I spoke with him after his talk. This post gives a quick overview of some of the key points I took away.

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ASH Exhibit HallIn recent years, there’s been a lot of progress in the treatment of chronic lymphocytic leukemia (CLL). New targeted therapies such as ibrutinib (Imbruvica) and idelalisib (Zydelig) have been approved and have helped extend the lives of patients with this disease further. However, there still remains a need for new treatment options.

Several new drugs are on the horizon for CLL.  At ASH there were a number of presentations for venetoclax, formerly known as ABT-199/GDC-0199, it’s a BCL-2 inhibitor, which is being co-developed by AbbVie and Genentech.  We’ve written extensively about it on the blog.  One of the challenges with venetoclax is the potential for Tumor Lysis Syndrome (TLS) – we heard at ASH that starting a patient on the drug needs to be carefully managed and monitored, with high risk patients hospitalized.

Other new drugs on the longer term horizon for CLL include acalabrutinib (Acerta) and BGB-3111 (BeiGene), both next generation BTK inhibitors and potential competitive threats to ibrutinib. The CLL market is becoming interesting again!

At ASH 2015, I spoke with Ian W. Flinn, MD, PhD. Director, Blood Cancer Research Program at the Sarah Cannon Research Institute in Nashville, TN. At ASH, Dr Flinn presented data for a CLL trial of venetoclax combined with obinutuzumab, a CD20 targeted monoclonal antibody; data was obtained in both the upfront and relapsed/refractory setting.

In a wide ranging conversation, we talked about some of the data of note in Orlando, what the future direction is in CLL, and what to look forward to at ASH 2016.

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ASH15 LBA Session

ASH 2015 LBA Session

The annual meeting of the American Society of Hematology (ASH) has a few quirks compared to other meetings. One of these is that all the “Late Breakers” are presented together on the last morning of the meeting.

It’s a rather unfortunate time given many have already headed back to their busy clinics or left for SABCS in San Antonio and ‘late breakers’ by definition, often offer new data that’s really noteworthy.

The result can also be a bit of a hodgepodge session that you have sit to listen through to get to those presentations you really want to hear.

At ASH this year there were two late breakers on new treatment options for CLL patients with a 17p deletion (Del17p). This is a pretty challenging group to treat.  Although ibrutinib is indicated for this patient group, many sadly relapse. There’s an unmet medical need for new treatment options. At ASH we heard data for idelalisib (PI3K-delta) and venetoclax (Bcl2).

After the session, I briefly spoke with Dr Kanti Rai (New York) for his reaction to the data. Dr Rai (pictured below) received the 2014 Wallace H. Coulter Award for Lifetime Achievement in Hematology.

Dr Kanti Rai receives 2014 ASH Lifetime Achievement Award

Dr Kanti Rai receives 2014 ASH Lifetime Achievement Award

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Whew, after posting the interview with Dr Tom Gajewski this morning from the American Association of Immunologists (AAI), we headed across town to the American Society for Gene and Cell Therapy (ASGCT) morning session and then dashed back to complete the first of the American Society of Clinical Oncology (ASCO) Previews for 2015!

What a busy week it’s been, never mind the hurly burly of today.

The ASCO 2015 abstracts went live at 5pm ET, with the exception of the late breaking abstracts, which are usually embargoed to the day of the actual presentation.

ASCO 2015 Abstracts

There are a number of topics well worth highlighting this year, so today kicks off the first of our annual Preview series on BSB. There will be much more to come – we wrote nearly 30 articles before, during and after the conference last year – this year will probably be similar with so much data to review and discuss.

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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A couple of years ago we had a lot of fun here on BSB following the progress of ibrutinib (Imbruvica), obinutuzumab (Gazyva), and idelalisib (Zydelig) in CLL and indolent NHL.  It seemed back then that the stunning trio were the hot topics for some time at ASCO and ASH meetings.  Exciting times!  All three target different entities (BTK, anti-CD20 and PI3K-delta) and made it past the tape to market, with Gazyva leading, Imbruvica a close second and Zydelig a slightly more distant third.  I was reminded of the race again over the last week or so as the 4Q earnings were announced, with Pharmacyclics reporting almost $500M for Imbruvica last year and estimating sales to hit $1B in 2015.  In contrast, Zydelig revenues for 2014 were $23M, reflective of their much later market entry in the US.

Still, that was a pretty impressive set of drugs all in development at the same time.

Two other agents we also reported on regularly were Infinity’s IPI-145, a PI3K delta-gamma inhibitor, and ABT-199/GDC-0199 (now known as venetoclax).  I haven’t heard much about the former of late, but after a few missteps, the next big question to consider is whether venetoclax is coming back strongly or destined for dog drug heaven?

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Readers don’t need Biotech Strategy Blog to tell them that Chimeric Antigen Receptor (CAR) T cell therapy (CAR-T), along with Checkpoint blockade, is one of the hottest areas of cancer drug development.

The last two days have seen pre #JPM15 deal activity with Kite Pharmaceuticals ($KITE) announcing a commercial collaboration with Amgen ($AMGN), which is not surprising given several of the Kite senior management team previously worked at the company.

Meanwhile, both Seattle based Juno Therapeutics ($JUNO) and Houston based Bellicum Pharmaceuticals ($BLCM) had successful IPO’s at the end of 2014. Interestingly, Bellicum are initially focusing most of their IPO funds, not on bringing their CAR-T to market, but on a novel cell therapy post stem cell transplant that aims to lower graft versus host disease (GvHD). GvHD is something we’ve been writing about regularly here!

Just this morning we’ve seen yet more CAR-T activity, with European Cardio3Biosciences (Euronext Brussels and Paris: CARD) acquiring the CAR-T technology of Oncyte (the oncology division of privately-held U.S. biotechnology company Celdara Medical).

There’s certainly a lot of activity in the CAR-T space and I expect we will hear more at next week’s JP Morgan Healthcare conference in San Francisco (#JPM15). One player in the CAR-T space who has not been gaining as much attention, and one that I think should not be dismissed, is Paris based Cellectis (Alternext: ALCLS.PA), who struck deals with both Servier and Pfizer last year. In June, BSB went to Paris and interviewed Chairman and CEO André Choulika, PhD and CSO Philippe Duchateau, PhD. At the recent American Society of Hematology (ASH) annual meeting in San Francisco, Julianne Smith, PhD (pictured below), Vice President CART Development at Cellectis, gave an in-depth interview to BSB. Dr Julianne Smith Cellectis ASH 2014 Interview Some key questions to address here are what are some of the important milestones for Cellectis in 2015 and and what makes the Cellectis CAR-T approach different from other companies in this space? Update Nov 7: This post now has two updates relating to the important news that came out after this post was published concerning the issuance by the USPTO of a gene editing patent that covers Cellectis’ intellectual property.  Subscribers can login to read more or you can purchase access by clicking on the blue icon below.

San Francisco – “Manic Monday” is what I call Monday at the annual meeting of the American Society of Hematology. It’s when the majority of oral presentations take place in multiple parallel sessions that require you to run between meeting rooms if you want to follow a particular drug across different blood cancers.

It’s even more challenging this year by the fact the conference is in three buildings at the Moscone Center in San Francisco. While Moscone North and South are interconnected thanks to an underground atrium, to get to sessions in Moscone West from North/South you have to go out of the building, cross one or two main roads, then go up elevators to the second or third floors. Not ideal! I think ASH is now too big for the venue.

Looking back on yesterday, it was a privilege to be in the audience when Dr Kanti Rai received a well-deserved lifetime achievement award for his work in chronic lymphocytic leukemia (CLL). A visibily moved Dr Rai was given a standing ovation by the thousands present in the plenary hall.

Dr Kanti Rai ASH14 LIfetime Achievement Award

Expect the #ASH14 Twitter stream today to be like opening the tap to run a bath. I congratulate all the hematology experts who have shared data and commentary from sessions via social media. #ASH14 stands out in terms of expert engagement and a high signal to noise ratio.

If there was an award for best conference coverage of #ASH14 on Twitter I would nominate @drmiguelperales.

Not only does Dr Perales from Sloan-Kettering share tweets from the sessions that he is in that are accurate and informative, but he frequently offers links to relevant papers for those that want to learn more. In addition to showcasing his expertise, this is a really good way to use social media to educate and inform. I look forward to his commentary, particularly if I am in another session at ASH. A must follow on Twitter!

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One of the things I most enjoy in cancer research is hearing wonderful patient stories from oncologists who are at the coal face of clinical trials. They get to deal with death and dying every day and like those in Pharma R&D, also live for the successes, the drugs that make it through pipeline despite great odds against them and make a meaningful impact on the daily lives of ordinary people.

We’ve all heard topline data presented at medical conferences around the world, but what the summary data can’t tell you is how a drug can impact people in ways that are clinically meaningful yet are more obtuse to capture in the aggregate. This is why case studies at CME sessions are increasingly popular, because they add value and context to common issues in a way that a Kaplan-Meier curve can never do.

Zydelig_logoWith the flurry of recent US and EU approvals for obinutuzumab (Gazyva), ibrutinib (Imbruvica) and the newest kid on the block, idelalisib (Zydelig), in CLL and indolent lymphomas, I wanted to take a look at these drugs from a different perspective.

A reader wrote in asking which of these new agents would emerge the winner and why?

Today’s post therefore offers some thoughts on the emerging CLL landscape now that we are shifting from new product development to the marketplace.

Drugs mentioned: Gazyva, Imbruvica, Zydelig, ABT–199/GDC–0199, Arzerra, IPI–145, CTL–019
Companies: Roche/Genentech, J&J/Pharmacyclics, Gilead, GSK, Infinity, Novartis

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Previously, we discussed the role of new agents being developed for aggressive non-Hodgkins lymphoma (NHL) with Dr Nancy Valente of Genentech, particularly how their antibody drug conjugates (ADCs) could have a potential role to play in revolutionizing treatment for patients with an otherwise poor prognosis.

The second half of the interview from ASCO 2014 focuses on more indolent disease, namely chronic lymphocytic leukemia (CLL) and the role of their novel therapeutics obinutuzumab (Gazyva) and ABT–199/GDC–0199.

We’ve heard a lot of positive data about the anti-CD20 monoclonal antibody, obinutuzumab, but the Bcl2 inhibitor undergoing co-development with AbbVie has had a bit of a chequered history to date. There is no doubt that ABT–199/GDC-0199 is highly potent, while lacking the severe myelosuppressive effects (thrombocytopenia) of its predecessor, navitoclax — which can be both a blessing and a curse — as the phase I single agent investigators discovered recently when severe tumour lysis lead to two sudden patient deaths.

It is important to address these issues expeditiously in a safe and rational way to ensure patient safety for those who enroll in both current and future trials. This is a critical issue we discussed at length with Dr Valente and how the company has been handling it.

At the AACR Molecular Targets meeting last November, many readers will remember that we learned about Genentech’s research plans for combinations with GDC–0199 in CLL and NHL in an interview with one of the scientists for that program, Dr Deepak Sampath.

Today, it’s time to look at where and how this exciting agent might impact CLL. Obviously, both CLL and NHL have commonalties and overlap, since they are both B cell disorders, so often what works in one disease often works well in the other too, as rituximab has clearly demonstrated.

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