Biotech Strategy Blog

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

Posts tagged ‘Genentech’

OX40 immune agonists at AACR 2016

British Javelin TrainIt’s Day 6 of our Countdown to the AACR 2016 annual meeting in New Orleans. We’re at the halfway, 6 posts written and 6 more to go!  Then it will be daily Live blogs from the meeting.

There’s a lot of cancer immunotherapy at AACR this year, so after yesterday’s post on GITR we’re continuing our mini-series with a look at another immune agonist.

Today, we’re moving onto OX40 (CD134) as a novel immuno-target. Regular readers will know that we’ve been following this target for some time.

Immune agonists such as GITR, OX40, CD40, CD27 and 4-1BB help to rev up T cells. As Dr Tom Gajewski (Chicago) told us last year, in an interview published on the blog:

…there are inhibitory receptors on activated T cells that are involved with shutting immune responses down. There are also activating receptors that help to rev up those T cells. You might question whether you can push an activator and block an inhibitor, and maybe get a good anti-tumor response going as well.

When we drive a car, we both lift our foot off the break and we step on the accelerator. We have really beautiful data in animals that that this is exactly the case, that if you hit one of those strong positive regulators, and block just one of the negative regulators, you can have complete disappearance of the tumors in mice.

Several of those positive agonistic antibodies against costimulatory receptors are in the clinic. One of them is anti-OX40 that a couple of groups have in the clinic. We’re working with Genentech, that has one of those agents in phase I.

What does the OX40 competitive landscape look like?

In those post we’ve provided commentary on some of the new products in development from companies and highlighted a surprising number of abstracts that you’ll want to watch out for at AACR 2016 if you’re on the cancer immunotherapy track.

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Beyond Blinatumomab – Update on Bispecific T cell Engagers

Washington DC Cherry Blossoms

Spring cherry blossoms

It’s twelve working days until the start of the annual meeting of the American Association for Cancer Research (AACR) in New Orleans. This is a meeting we’re especially looking forward to this year, not only for the cool science on offer, but also the Louisiana Coastal Cuisine!

Next year, AACR 2017 returns to Washington DC, at what hopefully will be a perfect time for cherry blossoms along the Tidal Basin.

In this post, I’ve taken a closer look at one cancer immunotherapy approach with new data at AACR – bispecific T cell engagers.  Amgen’s blinatumomab (Blincyto) is interesting because it was the first T cell engager antibody to be approved by the FDA for the treatment of Philadelphia-negative ALL and refractory B-cell precursor ALL, thereby offering proof of concept that such an approach could be safe and effective. There are, however, some challenges associated with it (which you’ll read about).

Can we improve on blinatumomab?

This post will address the question in three parts:

  • A look at what we know about blinatumomab to date
  • Where the competitive landscape is evolving with potential solutions
  • An interview with a scientist actively working in this field for their perspective.

For those attending AACR, I’ve put in links to some of the sessions and presentations to watch out for if you have an interest in bispecifics (there are a surprising number of them in R&D) – we’ll be writing more about some of the noteworthy data after it has been presented.

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Biotech Strategy Blog Mailbag Monday

Lindt Gold BunnyWhat questions are BSB readers sending in to us this month?

I wanted to take a moment out of AACR Previews and catch up on some recent news that is intriguing or perplexing subscribers. All questions are anonymous and in many cases, the same questions were actually sent in by multiple people, a testament to what’s top of mind in oncology lately.

Today, we cover a Q&A on a variety of topics on Kite Pharma (the Genentech collaboration and their TCR in solid tumours), a discussion about EGVRvIII in glioblastoma, and Gilead’s woes with idelalisib and an IO pipeline.

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Future of Cancer Immunotherapy Biomarkers

Biomarkers are a hotly debated topic at the moment within the cancer immunotherapy field.

At the recent Society for Immunotherapy of Cancer annual meeting (SITC 2015), there was even a debate with industry representatives arguing the “pros” and “cons.” Daniel Chen, MD PhD from Genentech (pictured right) argued “pro” and Steven Averbuch MD (pictured left) from BMS argued “con.”

SITC 2015 Biomarker Debate

The challenging question for anyone at the moment is if your Parent, Spouse or Best Friend were PD-L1 negative, would you still want them to receive a PD-1/PD-L1 checkpoint inhibitor (presuming it was indicated for the disease) and have a chance of a response, even if their PD-L1 negativity would suggest only a slim chance of responding?

AT SITC 2015 we spoke with an industry expert who offered insights into a leading company’s biomarker strategy and what the future may look like in 5-7 years time.

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Preview of ASH15 Late Breaking Abstracts

ASH 2014 San FranciscoThe 2015 annual meeting of the American Society of Hematology (ASH) (Twitter #ASH15) in Orlando has a bumper crop of interesting data.

ASH is one of the my favourite meetings on our conference calendar. I’ve been attending for many years, starting with when I was a commercial account manager for Hematology, Immunology, Transplantation and Oncology in the UK, then at Novartis in the US, when I was part of the team that brought Gleevec to market.

Hematologists make for an interesting group of people to talk to!  They are very focused on the science behind a disease and how translational research can move the needle forward and generate better outcomes for their patients.

As part of our continuing preview of #ASH15, I’ve taken a quick look at the late-breaking abstracts that were released today. We will have more in-depth coverage after we’ve heard the data presented in the 7.30-9.30 am session on Tuesday December 8.

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If you’re not already a subscriber, but what to know “What’s hot at ASH15?” then you should purchase access.  Additional ASH previews are already planned.  By the time you’ve read them, you should “hit the ground running” in Orlando.

As Warren Buffett famously said, “Price is what you pay. Value is what you get.” I couldnt agree more. We have subscribers who just purchase our ASH coverage every year, so do “check it out“ if you haven’t done so already.

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How do we boost the effectiveness of checkpoint inhibitors?

One thing has become very clear in the oncology space over the last year… checkpoint inhibitors are insufficient on their own for the vast majority of tumour types and patients that they have been explored in to date.  There are a number of reasons for this, but the main one is lack of T cells in the tumour, which enable an effective immune response to be mounted.

This begs the question – how can we address that issue and manipulate the tumour microenvironment in our favour, thereby making subsequent checkpoint blockade more effective?

There are a number of different ways to do this.

In the past, we’ve discussed several methods including innate immunotherapies such as Aduro’s STING or Biothera’s immunotherapeutic, Imprime PGG.  Other approaches include vaccines, which we have discussed in detail, t-cell receptors (TCR) or even monoclonal antibodies, such as AdaptImmune’s approach with their ImmTac technology.

There are other novel strategies currently being investigated by numerous companies too.

In this article – and also the second part of the latest miniseries – which will post tomorrow, we straddle our final reviews of interesting data from the European Cancer Conference (ECC) in Vienna with the upcoming one from the Society of Immunotherapy for Cancer (SITC) being held in National Harbor, Maryland.

Today’s post explores the concept of immunocytokines, engineered antibodies that are designed to boost the immune system, so that subsequent therapies will be more effective.

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Controversies in lung cancer immunotherapy

With the recent approvals of nivolumab (Opdivo) and pembrolizumab (Keytruda) in advanced lung cancer as well as new checkpoint inhibitor data presented on atezolizumab at the European Cancer Conference in Vienna, there are several new lung cancer immunotherapy controversies to consider such as…

  • How do we choose between docetaxel chemotherapy versus anti-PD1/PD-L1 immunotherapy?
  • Which checkpoint should we choose?
  • Is the PD-L1 biomarker useful and important?
  • Do the company assays differ?
Dr Jack West

Dr Jack West

Dr Jack West (Seattle) got the ball rolling on some of these issues earlier this month, generating quite a spirited and useful debate on Twitter, demonstrating that clinical decisions in this area are not as cut and dried as many might think.

In addition, we spoke to a number of lung cancer experts in Vienna for their perspectives on the data, the biomarkers, treatment paradigms and other critical issues.

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Is ocrelizumab a game changer in MS?

At the 2015 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting Barcelona on Friday, Dr Stephen Hauser (UCSF) presented the data for octrelizumab, an anti-CD20 monoclonal antibody, on behalf of the investigators in the OPERA trial.  This study compared octrelizumab to a standard of care at the time the study started i.e. IFN β-1a (Rebif).

Roche previously announced that ocrelizumab is the first investigational medicine to show positive pivotal study results in both relapsing and primary progressive forms of multiple sclerosis (MS):

  • Ocrelizumab showed superiority to interferon beta-1a (Rebif®) in two identical Phase III studies in people with relapsing multiple sclerosis (MS), the most common form of the disease.
  • Ocrelizumab is the first investigational medicine to show efficacy in people with primary progressive MS in a large Phase III study.

In addition, Dr Montalban presented the latest data for octrelizumab in primary progressive MS versus placebo (there are no approved therapies for this segment) on behalf of the ORATORIO investigators.

Here on BSB we have extensively covered other anti-CD20 monoclonal antibodies such as rituximab, ofatumumab and obinutuzumab in oncology indications specifically associated with hematologic malignancies, so what’s special about this same target and the results in MS with a different chemical entity?

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The value of BRAF targeted cancer therapies in lung and colorectal cancer

It’s time for the August mailbag where we answer questions about cancer research and R&D from subscribers.

After the recent queries about immuno-oncology, it’s time to focus a little on targeted therapies again. Neither chemotherapies nor targeted therapies are going to go away – they are still the bedrock of many treatment approaches in the clinic today. Sadly though, much of the new data for the latter trials were easily swamped by the sheer tsunami of immunotherapy data in Philadelphia (AACR) and Chicago (ASCO).

One important area that we have been discussing on both blogs for some time is the value of well designed basket trials.  It’s time to revisit this concept in the light of new data relating to the BRAF V600 mutation outside of metastatic melanoma.

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Will venetoclax impact acute lymphocytic leukemia?

We have followed the roller coaster development of the Bcl2 inhibitor, venetoclax (ABT–199/GDC–0199), for several years now.  There have been some lowlights along the way, but lately, things have been much rosier for AbbVie and Genentech as a more sensible dosing and patient management approach has been paying off.

Recently at ASCO and ASH, we have seen encouraging new data emerge in leukemia (AML and CLL), lymhomas (NHL), and even multiple myeloma.

New data has now emerged that looks quite interesting in another blood disorder. Today, we took a look at the data and also the potential implications for venetoclax’s development program.

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