Biotech Strategy Blog

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

Posts tagged ‘Cellectis’

Coney Island Roller Coaster

In the roller coaster of life that is oncology R&D, molecules come and molecules go… a rare few reach blockbuster heights while many others are quietly packed off to dog drug heaven, never to be seen or heard of again.

This is also very true of targets as well…

What about the in-between space?

Unfortunately, that’s where most molecules and cancer targets end up – into a deep black nothingness where we seek the high affinity targets with low grade side effects – and fall short in some way. It’s a frustrating place to be, to be sure.

One of these conundrums is compounds against CD123 (IL3Rα), which have been in the spotlight on and off this year and are turning out to be a rather mixed bag.

After our recent update on Cellectis and their CD123 direct CAR T cell therapy (UCART123), I wasn’t expecting to write any more on this until ASH in mid December. How wrong that prediction turned out to be!

Today we have quite a few things to discuss on this topic, so if interested in CD123 in hematologic malignancies and going beyond that to find better targets in AML then this is the poster for you…

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It’s been quite a roller coaster week so far for CAR T cell therapies, with Gilead announcing its intended acquisition of Kite Pharma on Monday.  If that wasn’t enough, Wednesday brought another surprise – the FDA approved a rare double header – for Novartis’s CTL019, now known as tisagenlecleucel (Kymriah) for pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL), as well as a new indication for Genentech’s tocilizumab (Actemra) for the treatment of CAR T cell-induced severe or life-threatening cytokine release syndrome (CRS) in patients two years of age and older.

Inevitably there has been much hullabaloo and much anticipation over the expected price tag that might accompany the first cell therapy product approved in the US. Whatever your view on this, many of us were no doubt relieved it came in under $500K ($475K, with no charge for the product in the first month if there was a manufacturing failure or no response).  While undoubtedly pricey, frankly it could have been a lot worse given the relatively small patient population.

Of course, the approved therapy isn’t the only expected high ticket item – there’s also hospital costs (including highly trained physicians and nurses), ICU costs (for very sick patients), supportive care costs (including tocilizumab if CRS occurs), not to mention any lab, diagnostic or monitoring tests required. All of these will no doubt push the total bill nearer to $1M.  In children though, the lifetime value of curative intent and many additional years of life is a much easier to grasp concept for payers than adding a few extra months at a high cost in adults.

These issues do raise the stakes for Kite and what they plan to do strategically in aggressive lymphomas, where there is a larger pool of eligible people for therapy, which must be offset by lower response rates (vs. pALL) and likely lower durability based on the data we’ve seen to date.  If we are truly moving into a world of value based pricing in the US, then efficacy and tolerability will ultimately have an impact on the perceived cost and value of treatment.

As Warren Buffett, the famous value investor has been want to say, “Price is what you pay, value is what you get.”

Whoa that’s a lot to think about – who knows what Friday may bring at this rate – and we still have the Kite Axi-Cel approval in aggressive lymphomas to go yet…

Meanwhile, there’s also a high unmet medical need for new effective treatment options in Acute Myeloid Leukemia (AML), especially in the relapsed/refractory setting, which is why we’re firm supporters of the Beat AML trial that the Leukemia and Lymphoma Society are pioneering. (See: Interview with Dr Brian Druker).

There’s also interest from several companies in a variety of novel targets, including CD123.

Notre Dame, Paris

Cellectis recently announced the enrollment of the first AML patient into their trial of an allogeneic CAR T cell therapy (UCART123) targeting CD123.

Quite aside from the issue of addressing whether such a product can be administered safely and effectively, one major why there is notable interest in Cellectis is because an allogeneic CAR T cell therapy offers the potential of a much cheaper off-the-shelf product as well as enhanced performance from an abundance of fit immune cells from healthy donors rather than tired or exhausted ones from people who are sick, thereby reducing the risk of manufacturing failure.

While in Paris, I spoke with Cellectis Chief Medical Officer, Loan Hoang-Sayag, MD about the trial design and CD123 as a target in AML.

This is the third and final post in our summer mini-series on gene editing and allogeneic CAR T cell therapy.

The first in the series featured an interview with Professor Waseem Qasim (Link), and the second with Cellectis CSO, Dr Philippe Duchateau (Link).

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Paris – amazingly it’s now 3 years since we interviewed Cellectis (NASDAQ: $CLLS) CEO André Choulika and CSO Philippe Duchateau (See post: Can Cellectis revolutionise CAR T cell therapy):

Cellectis CSO CEO

Cellectis Senior Management – Drs Duchateau and Choulika

Since then, we’ve followed the company over time, including an interview with one of their leading scientists, Dr Julianne Smith at ASH 2014, followed by the initial results of their first allogeneic CAR T cell therapy UCART19 presented at #ASH15 by Professor Qasim.

It’s hard to believe 3 years have gone by so quickly! As regular readers know what we often do on BSB is follow stories longitudinally, so while in Paris for an Immuno-Oncology Summit we thought it a rather timely opportunity to revisit Cellectis and take stock of where they’re at and ask what the future may hold for them?

With the recent news that Gilead have acquired Kite Pharma, there’s going to be a lot of interest in what companies such as Cellectis are doing to bring allogeneic “off the shelf” CAR T cell therapy to market.

This is the penultimate post in our summer mini-series on gene editing and allogeneic CAR T cell therapy and features a candid interview with Dr Philippe Duchateau, Chief Scientific Officer, at Paris based Cellectis.

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When we think of pioneers in the CAR T cell therapy space, one person who comes to mind is Waseem Qasim, Professor of Cell and Gene Therapy at the Institute of Child Health at University College London, and a Consultant Immunologist and Pediatrician at Great Ormond Street Hospital (GOSH).

Institute of Child Health

As readers may recall back in 2015, he gave the first allogeneic CAR T cell therapy under compassionate use to an infant with ALL, and in the process undoubtedly saved her life.

The subsequent case report published in Blood was the talk of 2015 annual meeting of the American Society of Hematology (ASH) in Orlando.

The poster focused on the first child that Prof Qasim treated and attracted a phenomenal amount of attention:

Prof Qasim UCART19 #ASH15 Poster

Where are we now with allogeneic CAR T cell therapy?

It’s been 18 months since we spoke to Prof Qasim, so while in London over the summer BSB caught up with him in his office at the Institute of Child Health.

This interview is the first in our latest 3-part mini-series on allogeneic CAR T cell therapy, which runs throughout this week. Here’s a teaser clip:

Kite’s first autologous product, Axi-Cel (in aggressive lymphomas), heads for regulatory approval in the US (PDUFA date November 29th), offering Gilead a hematology launch product with a high unmet need and, presumably, a relatively high price tag to match. Inevitably, some critical attention will subsequently be focused on the pipeline and whether they will move towards allogeneic CAR-T cell therapy (reduces cost of goods and increases profit margin) as well as how the TCR platform in solid tumours will fare.

It’s certainly a timely point to consider allogeneic CAR T cell therapies again given that things are rapidly heating up in the cell therapy niche following the Gilead announcement yesterday that they are acquiring Kite Pharma for $11.9 Billion.

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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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HMS VictoryThe dog days of summer are usually quiet on the Pharmaland front, although this year has been a bit of an exception, being notable for a batch of deals being completed and announced already.

The cell therapy space is one area that has courted both controversy and new collaborations, for example. Nary a week seems to pass without something appearing in the news! This has proven pretty interesting for a number of subscribers, who write in asking plenty of astute questions.

Today’s questions from BSB readers therefore encompass allogeneic cell therapies and what’s going on in that fast moving dynamic space.  Not all of the announcements may be what they seem though, and some are much more riskier than others.

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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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It’s that time of the month where the BSB readers get their chance to put us on the hot spot!

SITC 2015 Land GrabHere, we take a look at reader questions that have been submitted and argue the toss – is there evidence preclinically or clinically that is useful or instructive?

We can’t promise to answer every question, sometimes there simply isn’t any data to help either way.

This week, the topic is CAR T cell therapies, a subject that seems to be very high on many people’s minds and many of you had similar questions, so here goes…  

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The immuno-oncology space continues to get both interesting and also very crowded with over 20 chimeric antigen receptor (CAR) T cell therapies now in development. Originally, the excitement began with the University of Pennsylvania’s dramatic announcement regarding the first two advanced CLL patients they successfully treated, leading to a collaboration with Novartis and spurring a new ‘arms race’ development in this niche.

While most of the CAR T cell therapy data since has largely focused on acute lymphoblastic leukemia (ALL) and to a lesser extent, non-Hodgkins lymphoma (NHL), many have been wondering what was happening on the CLL front?  Has hope been abandoned there or will we see a renaissance occur?  It is of particular relevance with the Abbvie/Genentech announcement that venetoclax has positive data in CLL patients who have the Del17p mutation and filing is likely here in this subset soon.  Therapies such as ibrutinib and idelalisib are already approved in refractory CLL and may also have a future role to play here.

Do we need suicide switches for CAR T cell therapies such as Bellicum and Cellectis are developing or not?

Meanwhile, other hematologic malignancies are also being explored, including multiple myeloma. Why would a CD19 CAR work in a disease long considered to be CD19-negative in advanced, refractory disease?

Carl June UPenn

Dr Carl June, U Penn

What about progress with solid tumours? Many commentators and investors have been highly sceptical of the chances of success here following the advent of positive checkpoint data beyond metastatic melanoma and early CAR data in mesothelin cancers.

To answer these questions and also get a flavour for where things are headed with CAR T cell therapies, we recently interviewed one of the leading experts in this field, Dr Carl June (U Penn).

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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.

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