Biotech Strategy Blog

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

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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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New developments in renal cell carcinoma

Continuing our focus on genitourinary (GU) cancers this week, today we turn our focus from prostate cancer to renal cell carcinoma (RCC).

There were two important announcments on Monday this week relating to renal carcinoma.

Firstly, Exelixis announced positive top line data from a phase 3 pivotal trial of cabozantinib versus everolimus in relapsed metastatic renal cell carcinoma (METEOR).  The study met the primary endpoint (i.e. significantly improved progression free survival) and the company revealed the following data:

  • Cabozantinib reduced the risk of disease progression or death by 42%; Hazard Ratio = 0.58, (p < 0.0001) compared to everolimus
  • Interim Analysis of OS demonstrated a trend in favour of cabozantinib; Hazard Ratio = 0.67, (p = 0.005) compared to everolimus
  • Exelixis to complete US and EU regulatory filings in early 2016

Secondly, a press release from BMS highlighted the phase 3 CHECKMATE–025 trial comparing nivolumab to everolimus, also in relapsed metastatic RCC, where the independent Data Monitoring Committee recommended early stoppage on the basis of the primary endpoint (OS) being met. The company likely be seeking discussions with Health Authorities with a view to filing the data with the FDA and EMA.

There are some interesting points that fall out of these releases. To learn more, subscribers can log-in below or you can purchase a subscription in the box below.

With the launch of Episode 4 of the Novel Targets podcast today, I wanted to provide some more detailed background and a roadmap for this part of the journey for subscribers. There’s tremendous wealth of data now building up in several areas related to cancer immunotherapy and both interviewees, Drs Oliver Sartor (Tulane) and James Gulley (NCI), touched on many of them.

Thanks to Tom Gajewski’s exciting work, we can broadly think about different tumour types as inflamed (immunogenic) versus non-inflamed (non-immunogenic), which is a helpful starting point. Not all tumours thought to be responsive to immunotherapy will actually respond though, so we still have much work to do on the 70–80% of patients with solid tumours that don’t respond to these therapies.

Anyone who is interested can listen to the latest Novel Targets podcast.

The latest episode explores non-immunogenic tumours, using prostate cancer as an example. In the last third of the show, we do indeed talk about a promising new target that may have relevance not just to prostate cancer, but other tumour types too.

Listen to Episode 4  (open access thanks to our sponsors, Genentech)

BSB Subscribers can learn more in-depth information and insights about this emerging field by signing in or you can sign-up in the box below.

Last month’s Biotech Strategy mailbag – where we answer questions from subscribers – turned out to be rather controversial with strong feelings running in several camps on Puma Biotech’s neratinib in breast cancer.

This time around we have a bunch of questions on completely different topics and compounds to cover:

  • BRAF plus MEK and/or immunotherapy in BRAFV600 metastatic melanoma
  • Immunogen’s IMGN853 – now known as mirvetuximab soravtansine – in platinum resistant ovarian cancer
  • AbbVie/Genentech’s ABT–199/GDC–0199 venetoclax

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There can be no doubt that immuno-oncology is a hot topic in cancer research of late with checkpoint inhibitors, immune agonists, immunocytokines, CAR T cells, TILs, TCRs, not forgetting innate immunotherapies.  We’ve written extensively about many of these topics, but what about the companies behind them and their strategies?

One thing subscribers tell us they love reading about here on BSB is not only fireside chats with thought leaders, but also interviews behind the scenes with company personnel, be scientists, clinicians or CSOs.

Recently, we’ve posted some interviews with Roche and Genentech scientists/physicians about their IO platform that were well received. Today, it’s the turn of AstraZeneca and MedImmune, who are also developing checkpoint inhibitors and immune agonists against various cancers.

With the anti-PD1 antibodies i.e. Merck’s pembrlizumab (Keytruda) and BMS’s nivolumab (Opdivo) already approved by the FDA, and Roche/Genentech’s atezolizmuab well on the way to filing in advanced urothelial bladder cancer with the announcement this week that the IMvigor 210 trial in relapsed/refractory disease met its primary endpoint, the big question now remains is what’s happening with the fourth element of the quartet? How well is progress coming along there and what is the main focus we can expect in the near future?

Cambridge PuntingLike most Brits, when AstraZeneca noted back in 2013 that they expect to establish their global R&D hub in Cambridge, I assumed they meant in the Golden Triangle and not Massachusetts. This is a burgeoning area for European biotech research, which is somewhat ironic after the KuDos scientists working on olaparib (Lynparza) moved to Alderley Park in Cheshire with the acquisition and will likely face moving back again!

At ASCO, we had the pleasure of a chat with Dr Rob Iannone, the head of the AstraZeneca Immuno-oncology development program.  The company also published a number of interesting abstracts and posters that were on show in Chicago, as well as a burgeoning pipeline in this area beyond their lead compounds, the anti-PDL1 inhibitor, MEDI4736 and tremelimumab (anti-CTLA4).

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Over the last decade we have seen some real progress with some subsets of lung cancer, particularly in EGFR mutated and ALK translocated tumours.  Indeed, an incredible amount of translational work has emanated from just a few groups based in Boston, New York and Hong Kong.

Dr Jeff Engelman Source: MGH

Dr Jeff Engelman Source: MGH

At AACR earlier this year, Dr Jeffrey Engelman (MGH, Boston) gave a fantastic talk not just about heterogeneity, resistance mechanisms, but also on how lung cancer can transform. Included in his review was the role of biospies and how he sees those evolving.

I’ve been meaning to write up this important talk since April, but decided to wait until the key publications that were in press at the time were actually published – it was a longer wait than expected!

In general, it is our policy to write up published, rather than unpublished data, out of respect to researchers.  It also makes it more useful to readers when the translational and clinical data is publicly available for those interested in reading the in-depth research articles.  We also gathered commentary from other though leaders in the lung cancer space for some additional insights.

To learn more about the latest developments in the underlying complexity and clinical implications for EGFR+, T790M-positive and ALK-positive lung cancers, subscribers can log in below or you can sign up to read our comprehensive review of this topic.

Yesterday, Juno Therapeutics and Celgene announced a ten year collaboration that is expected to close in July-August.  In short, Celgene has exclusive right to entire the Juno portfolio in oncology and auto-immune cell therapy products in development outside North America and co-promote certain programs globally (not specified).  Juno, meanwhile, gains the option to co-develop and co-promote select Celgene programs (also not specified).

You can see the terms of the deal here.

And listen to the webcast from the call after hours.

This news comes hot on the foot of an earlier announcement that the FDA accepted the Juno IND for JCAR017, a CD19 CAR T cell therapy being developed in relapsed/refractory NHL scheduled to initiate in 2015, with the possibility of a registration trial commencing in 2016.

What was fascinating, however, was the BioTwitter reactions last night – predictably, people either loved or hated the news – it clearly came as a surprise to many.

This morning my inbox is full of questions on this dramatic topic from subscribers, so here are some topline thoughts on this issue to answer the questions coming in.

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2 Comments

Many years ago, I used to work in the sarcoma and GIST space, which is a very interesting and fascinating disease to explore from a biology perspective. There are many different subsets of sarcoma, several different histologies, as well as numerous targets such as KIT in gastrointestinal stromal tumours (GIST). Some of these subsets are sensitive to chemotherapy such as doxorubicin, while others such as GIST are sensitive to targeted therapies including imatinib, sunitinib, regorafenib etc. Imatinib (Gleevec) is particularly effective in GISTs with exon 11, while the less common exon 9 has been shown to be more sensitive to sunitinib (Sutent), for example.

Often pharma companies will work with the Sarcoma Alliance for Research through Collaboration (SARC) cooperative group to undertake a phase 1 allcomers trial to evaluate which subsets might be appropriate for a given therapy, before exploring a narrower inclusion/exclusion criteria in a larger phase 2 or 3 study.  You can check out their current clinical trials in sarcomas here.

Overall, people with malignant sarcomas tend to be seen by specialist centres where there are usually clinical trials available, representing a way to determine which of the agents in development are superior to the current standard of care.

Dr Margaret von Mehren

Dr Margaret von Mehren

One of my favourite moments at ASCO this year was escaping the heavily mobbed poster halls to sit down for a quiet ‘fireside chat’ and catching up with an expert in this field to learn more about the latest new developments in sarcoma.

I’m delighted to publish another thought leader discussion today on Biotech Strategy Blog (BSB), where we have an in-depth interview with Dr Margaret von Mehren, the Director of Sarcoma Oncology at Fox Chase Cancer Center.  She has spent spent her career trying to identify new therapeutics for gastrointestinal stromal tumours (GIST), as well as soft tissue sarcomas (STS).

To learn more about the latest insights on soft tissue sarcoma and GIST, you can log in or sign up in the box below.

In today’s post, it’s time to address a bunch of questions we’ve received over the last few weeks from subscribers about the latest and – not so greatest – in cancer research.

Chicago City View

ASCO 2015 Chicago

Sometimes these queries are fairly straightforward to answer, other times requires some sleuthing and hunting down thought leaders for some additional context and insights… For obvious reasons, these folks are best caught in person at cancer conferences such as AACR and ASCO.  The feedback isn’t always sparkly and positive though, it can also be gloom and doom, just like the inclement weather!

So here goes, questions on the following are covered in the article below:

  • Neratinib
  • Bavituximab
  • Gilead
  • Enzalutamide
  • MDSCs

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