Biotech Strategy Blog

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

Posts tagged ‘PARP’

A typical scene from ESMO 2019

Not in Madrid – Is it really only a year ago many of us were frantically dashing around at ESMO last year navigating crowded corridors, long queues for coffee, hunting down the last empty seat in jam packed halls, not to mention feeling the anticipation build for key data being presented in the Presidential sessions?

There are undoubtedly many advantages to virtual digital meetings, aside from the broader access for more people it provides and being able to see the slides unimpeded, yet it must be confessed the things I miss the most are the social interactions and catching up with people and their lives, however brief a moment it may be amongst the hurly burly of 20,000 other souls.

The cultural things we take for granted are often the very essence of what we miss most when they’re no longer obtainable.

Who truly would have guessed our world could be completely upended by the unexpected events of a global pandemic since then? In some ways, it has changed our perception of both time and space.

We have also seen some surprising changes in the fortunes of various clinical trials; some completely rational and predictable, others quite the opposite, as we learned yesterday in a very topsy turvy kind of way.

It’s time to discuss and review the highlights – and lowlights – from ESMO20 Sunday in part 2 of our daily coverage…

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Not in Madrid: The 2020 virtual congress of the European Society for Medical Oncology (#ESMO20) is underway and in this post we’re taking a look at some of the highlights from Friday at ESMO20, a day when we’ve seen a raft of posters and mini-orals released for on-demand viewing.

ESMO20 BannerWith COVID-19 rates rising across Europe, ESMO are to be congratulated for pivoting to a virtual meeting that allows the sharing of knowledge and advancement of the field. It was definitely the right decision in light of the ongoing travel challenges, quarantines, not to mention restrictions on large groups in many countries.

For our daily ESMO20 coverage – just as we would if we had been in Madrid – we’ve been listening to some of the on-demand mini-oral presentations and associated discussions, with a view to picking out and commenting on a few that stood out for us.

As always we’re approaching this from a cancer new product development perspective, and our choice is always a balance of emerging new targets and drugs, as well as following those we’ve previously written about.

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First in class or best in class?

Which paths will ultimately lead to success with novel targeted therapies?

Ah this question often seems a perennial one to consider at AACR annual meetings – and this year is no different in this respect.

Personally, to me, it doesn’t really matter what you claim aspirationally based on preclinical or even early phase 1 dose escalation data because… a lot can happen between then and later registrational studies.

Think about it carefully – weak efficacy, wrong tumour selection or setting, adverse event profiles, even narrow therapeutic windows can all too soon interfere and play havoc like a wrecking ball with many a well intended clinical program, especially once you start looking at combination strategies!

No, it’s not as easy as it looks sometimes.

In our latest AACR Preview series, we take a look at a number of targeted agents in development, many aimed at novel targets at are not run-of-the mill…

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Some of the upcoming coming small biotechs caught our attention and may turn out to be future stars

National Harbor – There were quite a few gems in the poster halls and oral presentations from up and coming small cap biotechs at the Society for Immunotherapy of Cancer (SITC) meeting this year.

Who were they and what did we learn from them?

In the latest part of our latest SITC coverage we highlight 13 presentations – 11 from small biotechs and 2 academic abstracts – that caught our attention, explain what’s intriguing about them and why they matter.

There’s not a single big Pharma included (unless as a reference point or given in combination) since the focus is mainly on up and coming companies with their novel approaches.

The list is quite selective and not at all random from a list of over 850 abstracts.

So what stood out and what was special about them?

Some of the selections are likely hidden sleepers that few will be familiar with… they also cover a wide range of approaches, targets, different modalities and even strategic intent.

Even if you were at the SITC 2019 meeting, increasingly there were more business meetings taking up valuable time than sessions attended, so this is a great way to catch all the highlights for your trip report 😉

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It’s the dog days of summer and yet there’s a lot happening on the DDR front from multiple angles.

After a short break from science, this makes now a really good time to reflect and take stock in order to explore some of the key issues facing the field, especially in terms of future combination approaches.

Research that’s appearing now may influence future trial designs – always a nagging worry in Pharmaland that the standard of care can change before you even get your own phase 3 readout! No one likes to be pipped to the post, after all.

With the early WEE–1 news this week and a raft of new PARP readouts, there is much to discuss and also plenty of nuance and subtlety to consider carefully because what looks obvious at first blush may not actually be the case based on prior evidence that many will have forgotten about.

So grab a cup of iced coffee and shades and settle down under your sunbrellas for a pleasant and easy to read review of the various trials, settings, combinations and DDR pathway considerations…

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Chinatown Chicago

One of the things we try to do on BSB is tread paths that aren’t well travelled.

It’s a bit like coming to Chicago and visiting areas such as Chinatown that are beyond the common tourist sights. It can take a bit of effort, but often delivers a memorable experience in the process.

In this final preview of #ASCO19 before the educational sessions start tomorrow, we’re offering up 10 abstracts that we think are underrated and noteworthy of closer attention.

Like any guide book our recommendations are subjective, but if you’d like to read more then subscribers can login or you can purchase access.

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Padstow, Cornwall – It’s May Day or ‘Obby ‘Oss, as it’s known locally in this little corner of south west England.  The quaint festival means that it’s the biggest day of the year as over 30,000 people crowd into the tiny fishing village.

Obby Oss Blue

Centuries old traditions are still alive and well in this part of the country and the big question of the day (are you red and white or blue and white?) is a far cry from the complex high tech world of cancer research.

Still, with all the time and attention focused on immunotherapy and targeted therapies of late, it is all too easy to forget what’s happening on the epigenetics front, which is quite a bit in practice.

We often see random allcomer approaches to clinical trials, which are find for phase 1 studies where you want to gather data on responders and non-responders in order to conduct PK/PD and immune profiling, as well as biomarker and signature development, but a potential recipe for disaster in phase 3 if you have no idea exactly what’s driving the efficacy since you can all too easily end up with unbalanced arms that you didn’t control for and thus skew your survival curves in a way you didn’t anticipate.

Why on earth would you use a targeted therapy in an untargeted fashion? Hmmm obvious question and yet, many companies still do this all the time.

There are some biotechs out there, I’m pleased to say, who do conduct extensive translational and biomarker research.  Obviously finding those markers is a lot more tricky than choosing red or blue.

One biotech company we have been keenly following for a while is Syros.

We first wrote about them in Spring 2014 and now, five years on, I thought it would be a nice idea to catch up with one of their founders and learn more about the science underpinning what they’ve done and where they’re going with future projects. Not only do they invest in smart medicinal chemists, profiling and translational research, but they also seek to identify rational reasons why people respond to their compounds.

The answers were rather interesting and there’s quite a bit that readers might be curious to learn more about…

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Beyond Loxo’s RET inihibitor, LOXO–292 in RET+ cancers, there were quite a bit of other targeted therapy data to mull over at ASCO this year.

ASCO18 Gems from Poster Halls

We highlighted a few of these in our Preview series in terms of what to watch out for, so I wanted to take a moment and explore some of them in a more detail now that the data have been presented.

Did they live up to the initial promise or not? What can we learn from trial failures? Sometimes this can be even more valuable than positive trials.

To find out, we took a careful at some of the readouts and assessed what looked better or worse than expected to help readers make sense of the tsunami of data that were presented in Chicago.

Inevitably, some of the selections we chose are gems from the poster halls

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It’s a Bank Holiday weekend on both sides of the pond, which is always a good excuse for some shorter snippets as everyone will be enjoying the break outside, weather permitting!

In our latest Preview series, we address some pertinent questions that have come in from BSB readers on several topics in between AACR and ASCO, including tumour mutation burden (TMB), the PACIFIC trial, monalizumab, renal cell carcinoma (RCC) and castrate resistant prostate cancer (CRPC).

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At the inaugural event in Orlando last year, one of the highlights for me was learning how important CD38 might turn out to be as another immune checkpoint target in combination with other approaches.

This year the meeting moved to the west coast and was held in San Francisco, making it the third one this month after JPM18 and GI18. Indeed, the fourth such event is also rapidly coming up with ASCO GU next month!

So what did we learn this time around? Quite a lot it would seem.

While much of the clinical data of late associated with immune checkpoint blockade (ICB) has been in metastatic melanoma and non-small cell lung cancer (NSCLC), two other tumour types that have received increasing attention in the IO space have been clear cell renal carcinoma (ccRCC) and prostate cancer.

There were a few interesting new things we can learn here…

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