Biotech Strategy Blog

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

Posts from the ‘Sarcoma’ category

Oncology R&D is very much a tale of two cities. At one end you have all big pharmas and biotechs with significant resources in the form of very large budgets, (hopefully) an extensive pipeline, plus many hands on deck to efficiently spread the workload, while at the other end you have what I call the ‘baby’ biotechs with completely the opposite situation coupled with a much greater need for prudence in how those scarcer resources are managed.

A failed drug development may not affect big pharmas very much, it’s written in to the strategic plans after all, and a 90% failure rate is very much de rigeur so you’re looking for the rare gems that will shine and carry the rest. In small biotechland, such inherent risks are much more prominent – and drastic – because a failed program can wipe out the stock overnight such that future endeavours to raise money are greatly hampered, putting the very life of the company at risk of not only delisting (if publicly traded) from stock exchanges such as NASDAQ, but also the ultimate doom.

The constraint that both bookends have in common, however, is familiar to many readers – how to get the best shots on goal given the time, energy, and resources available?

At BSB we don’t write just about big Pharma – we also try to highlight the roller coaster experienced at the other end of the spectrum and showcase some cool science in the process. Given our interest in stapled proteins as well as the various challenges associated with both tumour suppressors and MDM2, it seemed like a good idea to catch up with the folks at Aileron Therapeutics (NASDAQ: ALRN) and learn more about their progress since they combine all three elements in one go…. it’s time for some gems from the ESMO19 poster hall.

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Is the dragon roaring back?

It’s a while since we last looked at new developments in a rare group of cancers called sarcoma so this is a good time to stake stock and explore the positive and negative trial results, as well as look at some of the emerging targets that are being investigated.

Not all of them will likely pan out given the nature of the disease, but some might turn out to be hidden gems.

We’ve had a few negative trial readouts in sarcomas and plenty of new trials with a variety of agents in early development – is the dragon roaring back or whimpering?

Aside from our top 10 review, we also have a thought leader interview to share with commentary from a sarcoma specialist…

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Yesterday, we had a sarcoma expert in the spotlight looking at the new developments from the American Society of Clinical Oncology (ASCO).

In part two of our sarcoma mini-series, we have another interview for our readers, this time from the perspective of the CEO, Dr Carlos Paya. They had some interesting data in Chicago so what was their reaction to it and where are they going next?

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Sarcomas are a heterogeneous type of cancer that develop from certain tissues like bone or soft tissues such fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues.

Over the last two years, much has happened in this space so it’s an excellent time to revisit the niche and learn more about what experts think of the latest data that is emerging here.

We put a sarcoma expert in the spotlight and learned what their perspectives are on some of the emerging data in this niche as well as which ones offer hints of promise.

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After several years in the wastelands of cancer research due to lack of significant results and only one product on the market, therapeutic cancer vaccines now look to be back in fashion and are seeing a revival with their inclusion in clinical trials.

One of the reasons behind the resurgence of interest is the advent of checkpoints, and the potential of vaccines in the immuno-oncology space to boost or enhance the immune response.

Their use could not only increase the response to checkpoint inhibitors in people who might otherwise not respond, but in those who obtain some initial response such as a partial response, they could also potentially help achieve a more durable long-term response.

As we continue to ride the wave of cancer immunotherapy on BSB, the cancer vaccine field is suddenly an exciting area to watch.

I’ve long been known as a cancer vaccine sceptic, although recently several approaches in this niche have begun to look rather promising indeed.  Here, we highlight and discuss one such company in the field, including an interview with the CEO.

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Sarcoma is something we call one disease but actually represents 50-70 different histologies, which poses challenges for drug development.  Not only do you have to identify what’s the unique target, but it’s hard to accrue patients into trials, when a major center may only see a few of each sub-type.

Soft tissue sarcoma is an area of unmet medical need, and one I have been interested in since launching Gleevec in GIST (way back when) when I was fortunate to get to know many of the leading sarcoma experts.

Dr George Demetri

George D. Demetri, MD. Photo Credit: DFCI

One of these is Dr George Demetri, who is Director, Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute and a Professor of Medicine at Harvard Medical School.

At the recent European Cancer Congress in Vienna, I had the privilege to talk with Dr Demetri about some of the latest research in soft tissue sarcoma.

We spoke about cancer immunotherapy, new small molecules and monoclonal antibodies, and the potential of targeting the epigenetic machinery.

A lot of what Dr Demetri is doing is currently “under the radar” and while he didn’t give any secrets away, he did give some sense of where some breakthroughs may occur in the not too distant future.  He also talked about how sarcomas with a specific target can be used for proof of concept clinical trials of novel agents.

Given the pressure that many companies are under to speed up their path to market strategies, accelerated approval in a rare tumour subset is one approach that can be considered.

It’s an exciting time in the field with the potential for several agents in development to move the needle and make a difference. I hope you enjoy this post, it was a real pleasure to talk with Dr Demetri again.

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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).

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