Biotech Strategy Blog

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

Anyone who has been regularly to the American Society of Clinical Oncology (ASCO) over the last decade or two will have have sat through quite a lot of trials with doublets and triplets in numerous advanced solid tumours and seen an impressive graveyard of failed cytotoxics and targeted therapies build up… Too toxic, lack of efficacy, futile even. This is especially true for some of the more difficult to treat cancers such as pancreatic, small cell lung cancer, melanoma, glioblastoma and soft tissue sarcomas.

Chicago Riverwalk

ASCO 2015

There is hope though, after all, things have changed quite dramatically in the metastatic melanoma landscape over the last five years that it is now quite unrecognisable compared to a decade or even five years ago. This is very good news indeed.

What about the other tumour types in that list, though? How are we making progress with those?

In the latest series here on BSB, we’re going to focus on the new developments happening on the fringes of cancer research out of the main spotlight and look in more depth at what’s looking promising in some of these areas. Today, we’re going to start with small cell lung cancer (SCLC), a truly devastating disease with a horribly dismal prognosis.

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We’ve heard a lot about agents that target the PD–1/PD-L1 pathway over the last two years, in particular, from:

  • Nivolumab (BMS)
  • Pembrolizumab (Merck)
  • Atezolizumab (Roche/Genentech)
  • MEDI–4736 (AstraZeneca/MedImmune)

What about other agents against this pathway that are in earlier development? It really doesn’t take long for a new space to become quickly crowded and very competitive, as the Pharma R&D machines start cranking out results from clinical trials.

A critical question that will to be considered is how will the third, fourth or even 19th agent to market differentiate themselves from those already approved and established? Is it realistic to expect a blue ocean strategy approach or will the pieces of the pie become ever smaller?

At the annual meeting of the American Society of Clinical Oncology (ASCO) earlier this month, there was new data presented from other companies on checkpoint inhibition.  We took at look at some of the emerging data in more detail.

To learn more about the increasingly competitive anti-PD1/PDL1 pathway market, check out our insights in the mini report below.

One interesting aspect of the recent American Society of Clinical Oncology (ASCO) meeting was the surprise many people expressed in conversations that chemotherapy might actually be useful in combination with checkpoint inhibitors.

You see, several years ago when we first started writing about this new class of agents, I remember vividly how quite a few analysts grumbled on social media or sent me snarky personal messages when it was even suggested that this — along with combinations with existing targeted therapies — might be a worthwhile and valid approach to explore. Clearly they believed that immunotherapies (as monotherapy) were going to be the ultimate panacea.

Not so fast…

There are a number of scientific reasons for combination strategies, but not everyone thinks rationally when new approches come along and their attititude is often ‘out with the old, in with the new!’ It was actually quite amusing to see some of the very same folks in Chicago now eulogising the combination of checkpoint blockade with… chemotherapy in lung, colorectal or even bladder cancer.

One reason why these traditional therapies may be important is because they can influence the tumour microenvironment in both positive and negative ways. That can be helpful for deciding on rational future combinations, rather than just throwing mud at the wall and hoping based on a limited set of data.

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Chicago – it’s Monday at ASCO 2015, with a full day of symposia, oral abstracts and posters here in Chicago.

Yesterday in the Plenary Session here at ASCO, Dr Jedd Wolchok (Memorial Sloan Kettering Cancer Center) presented the results of the Checkmate 067 trial (LBA1) – the results of a phase III trial of nivolumab (NIVO) alone combined with ipilimumab (IPI) versus IPI alone in treatment naive patients with advanced melanoma. You can read more about this in our ASCO Day 3 highlights.

Dr Wolchok is pictured below, prior to presenting at the ASCO 2015 press briefing.

Dr Jedd Wolchok ASCO 2015 Press Briefing

Checkpoint inhibitors have been a real buzz at this meeting, but with the realization that they are not going to work in all patients, and other treatments are not going away… for all the promise there’s still a lot of work to do optimize cancer immunotherapy.

There’s also been a lot of talk at ASCO about PD-L1 as a biomarker, and if you haven’t already done so, do check-out Episode 2 of the Novel Targets podcast (The Immune Biomarker Show) that touches upon many of the key issues.

If you haven’t already done so, do check out yesterday’s post on the metastatic lung cancer session, including the AZD9291 vs. rociletinib race to market in T790M, because there was some interesting new data presented that will likely have an impact today.

What’s hot on Monday at ASCO 2015? This will be the last of our daily posts from ASCO 2015. Subs can login to read our highlights as the day progresses. We’ll update schedule permitting.

Chicago – the cancer immunotherapy poster session yesterday morning was “mobbed,” that is the only word to describe it. I have never seen such a crowded poster session at any medical meeting before. It speaks to the huge interest in this growing field.

ASCO 2015 Cancer Immunotherapy Poster Session

It’s also a reflection that insights into the future direction of the field will be found in posters about preclinical and early work, rather than in oral presentations that reflect strategic decisions made a long time earlier.

We know checkpoint inhibitors work in many cancers, and a few more have been added to the list at this meeting. While that’s interesting, the real question is how do we increase the response rate and also get them to work in non-immunogenic tumors?

Yesterday in the poster session at ASCO, there was a poster that caught our attention on one approach that may achieve this. We briefly wrote about it in the ASCO Day 2 blog.

Also of note yesterday was that the new generic name for the PD-L1 checkpoint inhibitor from Roche/Genentech. MPDL3280A is now atezolizumab. A few presenters stumbled over the pronunciation, it was so new…… and all the z’s add to the trickiness!

As to what Day 3 at ASCO holds, we’ll be updating this blog during the day as our schedule permits.

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Chicago – after an evening of beer and networking at the unofficial ASCO15 Tweetup, the ASCO annual meeting, like a checkpoint inhibitor combination, releases the break and steps on the gas: the main data presentations start today. It’s “super saturday” at ASCO15.

Yesterday, the press had a preview of some of the cancer immunotherapy data to be presented this morning – we’ve shared our preliminary thoughts on this in yesterday’s ASCO15 Day 1 Cancer Immunotherapy post.

ASCO 2015 Day 1 Highlights

So what’s hot at #ASCO15 today?

We’ll be doing a rolling post throughout the day – when the opportunity presents we’ll provide some topline thoughts on sessions we’ve been to.

If you are here at ASCO, one #ImmunOnc presentation to watch out for this morning is the David A Karnofsky memorial award and lecture being given by Suzanne L. Topalian, MD in the main plenary hall (N Hall B1) at 11am.

From the recent presentations we’ve heard from her at AACR and AAI, her lecture entitled, “PD-1 Pathway Blockade – a Common Denominator for Cancer Therapy” should definitely worth listening to!

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Chicago – the 2015 annual meeting of the American Society of Clinical Oncology (ASCO) is underway. It’s the Super Bowl of clinical cancer research with approx 35,000 attendees from all over the world.

Earlier today, in a press briefing focused on cancer immunotherapy, we had a glimpse of some of the data that ASCO thinks is particularly newsworthy at the meeting.

In this post, we’ll offer some top-line thoughts and commentary on the following presentations by:

Dung T. Le “PD-1 Blockade in Tumors with Mismatch Repair Deficiency”

Anthony B. El-Khoueiry “Phase 1/2 Safety and Antitumor Activity of Nivolumab in Patients with Advanced Hepatocellular Carcinoma (HCC): CA209-040

Tanguy Y. Seiwert “Antitumor Activity of the Anti-PD-1 Antibody Pembrolizumab in Biomarker-Unselected Patients with R/M Head and Neck Cancer: preliminary results from the KEYNOTE-012 Expansion cohort.”

Luiz Paz-Ares “Phase III, Randomized Trial Checkmate 057 of Nivolumab (NIVO) versus Docetaxel (DOC) in advanced Non-Squamous (non-SQ) cell Non-small Cell Lung Cancer (NSCLC).

We’ll be writing a daily post from ASCO 2015 with regular updates on sessions we’ve attended, and initial thoughts and reactions. Our usual in-depth coverage will follow after the meeting.

ASCO 2015 Special Awards

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Yesterday, Juno Therapeutics announced a new deal for a collaboration with Editas Medicine that is:

“Focused on creating chimeric antigen receptor (CAR T) and high-affinity T cell receptor (TCR) therapies to treat cancer. The companies will pursue three research programs together utilizing Editas’ genome editing technologies, including CRISPR/Cas9, with Juno’s CAR and TCR technologies.”

This follows on from their recent deals with Fate Therapeutics and Stage Cell Therapeutics and bluebird bio’s licensing deal with Five Prime for novel antibodies to develop CAR T cell therapy.

One of the most interesting questions in CAR T cell development, is whether you need to incorporate a suicide gene or suicide switch into them that allows you to turn off the response, force the T cells to self-destruct, in the event of severe Cytokine Release Syndrome (CRS) or other serious adverse events.

This review article is another example that straddles data from conferences earlier this month at Immunology 2015 (AAI) and American Society of Gene and Cell Therapy (ASGCT) with the American Society of Clinical Oncology (ASCO) this coming weekend.

At ASGCT we spoke with Dr Carl June and also heard the latest update on what Cellectis are doing from Dr Julianne Smith.

Companies mentioned: Juno Therapeutics, Novartis/U Penn, Cellectis, Bellicum, bluebird bio, Formula, Molmed.

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Have you ever sat in a freezing cold scientific session and been so engrossed in the compelling presentations that followed, you simply forgot to take notes? Not one. That actually happened to me at the American Association for Cancer Research (AACR) in Philadelphia this year in one of the many fringe sessions that I attended.

Reading Terminal Clock

Reading Terminal Clock, Philadelphia

Granted, the hot topic of the conference was undoubtedly checkpoint inhibition, but I was anxious to escape to the comfort of some meaty and familiar basic and translational science, namely MYC.  MYC is largely thought to be a difficult to target, even undruggable protein, and along with RAS and p53, represents a formidable challenge for cancer researchers.  These three oncogenic proteins alone are probably responsible for more drug resistance developing and even death from cancer than any other proteins in a patient with advanced disease.

For cancer patients with advanced disease, the clock is ticking on time they have left.

Solve these three problems (MYC, RAS and p53) and we may have a shot at dramatically improving outcomes. As Dr Gerard Evans (Cambridge) noted:

“I think it’s fair to say that we don’t really know why interruption of any oncogenic signal actually kills cancer cells, but one of the reasons that we’re interested in MYC is because it seems to be a common downstream effector of many, maybe all cancers.”

Sure, the road to success is paved with an enormous graveyard of failures, just as metastatic melanoma was before checkpoint blockade came along, ironically.  What I heard at AACR both inspired and filled me with greater confidence… we’re finally getting somewhere.

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Multiple myeloma (MM) has been very much in the news this week after the American Society of Clinical Oncology (ASCO) abstracts were released to much anticipation.

Myeloma is largely thought to be an incurable disease despite the option of an autologous stem cell transplant for newly diagnosed patients. That said, I have actually met some people who have had two or 3 transplants over several decades, a testament to their strength and fortitude in enduring such a challenging procedure.

This year, the news media have focused on elotuzumab (BMS/AbbVie), a CS1/SLAMF7 inhibitor that has previously shown clinical activity in earlier trials, after it was showcased in the ASCO Presscast last week. This why you see many articles on the data reported from this particular abstract.

New Orleans American QueenIt’s not the most exciting new data in this disease for me though, that honour goes to two other therapeutics of an entirely different kind. They come completely out of left field and what we saw over the last two months really caught our attention and may surprise you too.

Indeed, we saw hints of some of this data at the American Society for Gene and Cell Therapy (ASGCT) meeting last week in New Orleans.

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