Biotech Strategy Blog

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

Posts tagged ‘ovarian cancer’

There’s more than one way to look at data despite the same top line results

Beyond the obvious, what else was coming out at ASCO this year?

It’s time to divvy up the spoils and explore some intriguing trial results not in the mainstream consciousness.

Well there is one major trial we critique in this latest review, although perhaps with a rather different take on the data as it could be considered in a more controversial light when you look at the details.

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Time for some commentary and review of ESMO highlights and lowlights from Paris

One of the fascinating aspects of the PARP inhibitor niche is how often the results across several different company trials have gone the same way more often than not.

This has been a rather unusual streak, let’s face it.

At some point I was half expecting the wheels to fall off the wagon and the trend to be bucked, to much consternation from outside observers.

It’s already starting to happen, although perhaps not in the way we might have anticipated.

After all, you can’t enroll patients willy nilly and expect to see a positive result every time because patient selection can and does matter over the long run.

Here, we discuss some of the emerging controversies coming out from ESMO…

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Garden of the Gods

This post is about some of the trials and tribulations around oncology R&D and how we have gone from broad targeting of a particular process to honing in on what basically represents a novel target in a much more selective and precise fashion.

It’s a bit like the difference between a blunderbuss versus a sniper’s rifle – you can induce a scattered or a narrow effect, and hopefully reduce unwanted toxicities in the process too.

Targeting achilles heels and vulnerabilities in the cancer cells are not new, but figuring out novel synthetic lethal pairs could well be key in terms of a failed trial versus a successful one.  These days, more and more companies are abandoning the dreaded catch-all phase 1 polyglot trials – aka refractory advanced solid tumours – for ones based on a more rational approach dictated by the science and underlying biology.

I’m delighted to see this trend emerge and hope more will continue.  After all, if you have a targeted agent why treat it in a nihilistic and un-targeted fashion, subjecting patients who have absolutely no hope of responding to Compound X to unwanted toxicities, when they might well have a better shot at an entirely different approach?

Without much ado, it’s time to focus on the novel oncology target – and yes, there’s a couple of early frontrunners already…

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Is the early stage cell therapy landscape bleak or promising these days?  Perhaps it depends on which angle you look at the question.

Originally, I had planned to cover five preclinical cell therapy companies we hadn’t covered before, although this ended up as six with five intriguing ones, one I’m not a fan of, plus some additional really intriguing academic research in preclinical development, which may have some broader clinical applications many may have not realised yet.

We also highlight some emerging trends in this niche as early stage companies learn from what has gone before and begin to adapt their pipelines to address the challenges rather than merely be yet another me-too CD19 CAR whatever.

This inevitably means the emergence of new targets, modalities, technologies, and approaches…

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It’s time to look at progress on the ADC front, something we sporadically cover where there are new phase 1 or 2 data of note.

Making waves in the ADC niche

Compared to the myriad of targeted small molecules and IO therapies out there, ADCs and related drug conjugates form a much smaller class of agents, although this is slowly changing as the technology develops on several fronts.

Yesterday’s first plenary session at the 2021 Targets/Triple meeting focused on new developments in tumour-targeted conjugates including a couple of early stage projects, which should be well worth watching out for and following over time.

It wasn’t all plain sailing, however, with plenty of important caveats and nuances to be aware of…

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Every year the sweet spot sandwiched between AACR and ASCO comes around all to quickly, as we’re wrapping up interviews conducted at one and preparing the previews for the other, never mind ESMO Breast, AAI, and ASGCT all coming in May as well.

Cambridge Botanical Gardens

This year is no different and I’m delighted to say they segue rather nicely for once!

It’s hard to believe we’ve been writing about DNA damage repair and PARP inhibitors since 2008/2009 or so, and still this topic just keeps growing and growing!

We’ve certainly come a long way since those early days and now the broader DDR niche is also expanding as more targets are identified and evaluated, both in animal models as well as the clinic.

This list will also increase as CRISPR screens continue to identify synthetically lethal targets – some will be useful, others will fall by the wayside due to lack of efficacy or poor tolerability. Finding a balance between the two will therefore be a big key to success.

In this post we’re going to start with an update on the PARP1/2 inhibitors then catch up on data from other DDR family targets and finally explore a pipeline discussion with an industry expert who is well versed in the DDR field.

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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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Part of the next wave of early immuno-oncology agents are focused on addressing the tumour microenvironment and inhibitory factors that dampen down immune responses.

As we look at all the options available, there are a few obvious ones such as physical barriers and inhibitory cytokines or chemokines, but beyond that are a vast array of other potential targets we can aim at therapeutically.

We have covered quite a few of these already, but here’s a new one to add to the list.

One particular advantage is that because it is early in development, few competitors have cottoned on to the concept yet. First mover advantage can have quite a few benefits, after all.

Here’s an important question to consider in terms of oncology R&D – would you rather explore a blue ocean strategy or follow the lemmings off the cliff and be 14th to market in a highly competitive red ocean?

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The calm before the morning storm surge at ESMO19!

Barcelona – I can’t recall the last time we published three long form posts from a conference before high noon (US time) on the same morning, but that certainly illustrates how busy this year’s ESMO is and there’s a lot more to come yet.

The initial starting coverage for today includes hot topics in ovarian, lung, and colorectal cancers and more will be added in due course.

If you are looking for osimetinib in FLAURA and AMG 510 in KRASm colorectal cancers, click on the BSB log in the top left corner to check out the front page slider for more information on those write-ups and commentary!

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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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