Biotech Strategy Blog

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

Posts tagged ‘Breast Cancer’

ADCs – Controversies, Challenges, and Opportunities

The romantics wearing rose tinted glasses might well think of successful cancer drug development much like the famous poem by Lord Byron;

“She walks in beauty, like the night
Of cloudless climes and starry skies”

Yet the reality is much more opaque with endless cloudy or wet days and foggy nights much more typical than the exception.

There are often unexpected glitches in the form of serious adverse events, drug interactions, biomarker crashes, narrower therapeutic indexes and poor activity.

None of this stops a raft of companies rushing into a niche when it is suddenly declared ‘hot’ and everyone wants a piece of the action.  This creates an entirely different series of issues to tackle such as acquired resistance and cross resistance.

Some of the numbers in this latest research surprised me and left me pondering a series of provocative questions such as who’s going to stand out from the crowd, who is going finesse things in the clinic – and most importantly – who’s going to break the mould with a different approach?

In this article we explain some of the nuances at play and offer some pointers of new directions the field is taking, not all of them, I’m sorry to say, are for the better…

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Cut and run

Sometimes it’s the unexpected or quirky changes that stand out

While many observers have almost exclusively focused on protein degradation in the context of modern chemical proximity approaches, this isn’t the only possibility when using a bifunctional small molecule.

Indeed, I would argue some of the most creative ideas we are seeing coming out of late may well turn out to be unexpected standouts in future clinical trials.

Yet their goal is a very different one from what we’ve seen from the majority in the clinic.

In this latest example of the genre, we turn our attention to an area where drug hunters have struggled to find solutions for, despite the challenge being a commonplace issue for many oncologists in the clinic…

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ESMO22 Preview 1 – what to watch out for in breast cancer

Time to make your selections!

This year seems to be going all to quickly as we have arrived in time for the annual ESMO Preview series.

This year we have a lot of topics to cover from a review of various solid tumour types, novel targets and developmental therapeutics, hematologic malignancies, as well as various IO and cell therapy related readouts.

As always, the goal of our previews is to not only provide some context for what to expect, but also to highlight potential success and failures since not all of the trials have been headlined by the companies concerned.

It’s all to easy to forget agents in the same class of therapeutics can produce quite different outcomes despite similarly looking trial designs, as we will find out…

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The long and winding road to success

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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Can we predict response to breast cancer therapy?

It’s time for some breast cancer highlights where we look at some of the key findings from the first day of the annual SABCS meeting.

Order from chaos

There were a number of key talks to think about with two particularly outstanding presentations of interest to many BSB readers because of the potential implications of the research…

Importantly, how do we go about finding deeper patterns in large datasets rather than merely looking at the top line clinical findings in the ITT population and treating everyone the same?

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Is olaparib scaling new heights in OlympiA?

Source: Wikipedia

We first wrote about the fascinating and complex space way of synthetic lethality and PARP inhibition way back in 2006 when the early preclinical developments and targets were just emerging and finally here we are – 15 years later – with the very first phase 3 data in the adjuvant setting.

It’s not often I get to highlight someone and their extensive research from my alma mater, but it’s a delightful opportunity to put it on the front page for a change. The gritty urban setting is a far cry from the romance of the other Kings College (in Cambridge), although the two cities do overlap somewhat in this particular story.

What can we learn from the latest clinical development in early stage breast cancer and what don’t we yet know?

There’s actually quite a lot to ponder and digest here…

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Tooting the DDR horn

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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A case to answer

Every now and again something intriguing comes along, which generates a flurry of interest from our readers in terms of early stage pipeline developments.

This example is no exception to the rule, judging from the enthusiastic questions we’ve received over the last couple of months.

Wit a raft of new clinical data available there’s a clear opportunity to explore exactly what’s what and is there something special coming along or is there a real risk/worry this might turn out rather like the IDO pathway with mixed red and green signals floating around?

The only problem here is after carefully reviewing all the evidence I found myself firmly in the sceptics/bear camp, at least for now.

It’s time to walk you all through what we found and what it all means…

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Finding success in hard to treat breast cancers

Finding pathways to success in breast cancer

The last week brough a huge tsunami of data across varied topics ranging from hematologic malignancies (ASH), breast cancer (SABCS) and immunotherapies (ESMO IO) – we’re still digging our way out of it all!

There’s plenty of detailed analyses yet to come from all of these meetings, including some KOL interviews and thought provoking pieces to consider as well.

Here we look at some translational findings from academic researchers as well as companies involved in clinical trials in breast cancer. Yes, it’s time for some post SABCS reviews on a series of different topics…

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A phoenix rises from the ashes

A phoenix rises from the ashesResilience in purpose and openess in strategic direction are key dual features in the DNA of strong biotechs which succeed in the long run and live to survive the roller coaster ride that is oncology R&D.

Setbacks are to be expected, but what matters more is not that they happen, but the mettle and toughness to deal with them over time.

There is no doubt Clovis Oncology encountered a major setback with the abandonment of rociletinib in lung cancer, while the rise of PARP inhibitors meant they were well placed with the rucaparib development.

Beyond these events, what next?

It’s time to take a bigger picture look at what’s happening with the pipeline and where they might be heading since there could be some surprises in store…

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