Biotech Strategy Blog

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

Posts tagged ‘talazoparib’

Changing of the guard

A frequent challenge in oncology R&D is the fast paced nature of pipeline development such that there’s always something cool or new coming along nipping at the heels of those further ahead in clinical development coupled with the changing of the broader landscape before you even get to market.

What this means is companies with agents in phase 2 development can frequently feel rather squeezed between the two extremes.

This can lead to a lot of pondering on whether they will have enough innovation to make an impact on whatever are the favoured approaches by the time they might get to market, while at the same time offering sufficient protection against the novel compounds coming along behind.  Obviously no one drug is perfect and each will have their own achilles heels, to add to the mix and uncertainty.

For some time now there hasn’t been much in the form of new approaches in prostate cancer beyond the myriad of androgen receptor antagonists in various treatment niches plus the PARP inhibitors in a select population of men with BRCA mutations… what then?

A big question targeted therapies often have to address is their impressive initial response rates and PFS based on RECIST measurements don’t always translate into people living longer, as measured by overall survival.  No drug is without toxicities either, which means these need to be factored into the final clinical decision making and can make or break early uptake more than initially realised.

In our latest review we highlight some examples of where the field might be headed next (or not), based on some new preclinical and clinical data presented…

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New directions in small cell lung cancer

Linie 30 Florisdorf, Vienna

With all the frequent attention on lung cancer of late – mostly on the most common form, non-small cell lung cancer – it’s easy to forget small cell lung cancer (SCLC) in the rush to highlight new developments.

It’s time to talk turkey about old and new agents in the quest to improve outcomes for people with this dismal disease.

The good news is there are also a raft of scientific developments emerging, which may potentially help us better identify discrete subsets and enable the matching of appropriate regimens to the underlying biology.

At the World Conference in Lung Cancer this week in Vienna we’ve been following the numerous trials (and tribulations!) of progress in this niche, with a look at several key readouts through the lens of a thoracic lung cancer specialist.

What does he have to say and where are things heading next for the field?

To find out more, check out the interview below…

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How – and when – should people with early stage breast cancer be treated with a PARP inhibitor?

We’re going to take a change of pace from our scientific previews from the forthcoming AACR meeting and switch to early stage cancer clinical trials readouts coming out this week.

The first one on deck is an update of the OlympiA trial exploring the PARP inhibitor olaparib as adjuvant therapy after chemotherapy in early stage germline BRCA mutation-positive (gBRCAm) high-risk breast cancer.

This is an important trial to follow given it’s the first of the PARPs to read out in early stage breast cancer in a well defined patient population with a high risk of disease recurrence.

Here, we explore the pros and cons of the latest findings and also put them in context since there’s quite a few important nuances to consider…

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Pulling a rabbit out of a hat

It’s time to tackle some controversies in advanced prostate cancer and look at exactly who’s pulling a rabbit out of a hat?

At ASCO GU we saw new phase 3 data from the 1L metastatic castrate resistant prostate cancer (mCRPC) setting with very different results produced for olaparib and niraparib, generating quite a bit of debate.

Here we explore half a dozen key issues in the context of both trials and look under the skin at the important subtleties and nuances to think about…

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Endless DDR changes and how we are going beyond PARP inhibitors

There are at seemingly endless genes associated with genomic instability and the development of cancer – there are at least 450 genes associated with DNA Damage Repair (DDR) alone, for example.

This means it is, perhaps, not at all surprising these can not only induce significant changes in various tumours, but they also might have deeper interactions between them as well, many of which we may not yet know about.

Just as we have seen some success with PARP inhibitors in patients with BRCA loss of function, so too are companies seeking to exploit additional vulnerabilities by targeting the achilles heel with other paired approaches such as ATR inhibitors in cancers where there is ATM loss of function.

There has been a raft of data in this niche from several agents in this class so it’s time to turn our attention to reviewing what we learned from the many subtleties and nuances that inevitably abound in this DDR subniche, including recent data presented by Repare Therapeutics at the AACR-NCI-EORTC meeting…

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When PARP and immunotherapy worlds collide

Picking a PARPi – what can the biology tell us?

How many observers realised there’s more than one member of the PARP family?

There’s quite a bit to be learned in the DNA damage repair (DDR) and replication stress niche, especially when it’s new targets, new tumour types and even new companies to look at.

In our latest post on this space we switch horses from big Pharma and continue the story with some interesting findings from the biotech side of the R&D fence.

This is a key trend we’ll be following going into ASCO next month as we start to see the layers peeled off the onion and get a lot at what’s working, where it’s working and just as importantly, what’s not…

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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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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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ESMO20 Preview 4 – Targeted therapies to watch out for

Not in Madrid – with the global pandemic continuing to exert a significant effect on the cancer conference season, the annual meetings continue apace virtually.

Plaza de Cibeles, Madrid

For this year’s ESMO meeting we have already covered immunotherapies, both early and late stage pipeline highlights and now it’s time to explore what to watch out for over the weekend on the early to mid stage targeted therapy front.

The good news is there is some potentially practice changing data being presented, as well as some novel approaches in preclinical development emerging. These should be hitting the clinic in the near to medium term future.  On the other extreme is the more common problem whereby a few agents are showing signs of not holding up to their early promise/hype.

Let’s now take a look at what we can learn in the fourth and final ESMO Preview for 2020…

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Flying high in the DDR oncology niche

Recently, PARP inhibitors have been back in the news for several reasons, including the publication of the olaparib (AstraZenca/Merck) advanced mCRPC data in the New England Journal of Medicine from the phase 3 PROfound trial and the announcement regarding achievement of the key secondary endpoint of overall survival. As Dr José Baselga quite rightly noted, this is very good news indeed because:

“Overall survival in metastatic castration-resistant prostate cancer has remained extremely challenging to achieve.”

We’ve rather more trial misses in this disease setting than successes from various therapies over the last few years including ipilimumab, PROSTVAC, alisertib, and atezolizumab, to name a few off the top of my head.

Related to mCRPC, let’s also not forget the upcoming PDUFA date later this month for Clovis’s rucaparib in the very same indication.

Not to be outdone on the PARP front, just a few days GSK received FDA approval for niraparib as first-line monotherapy maintenance therapy for women with platinum-responsive advanced ovarian cancer – regardless of biomarker status – based on the phase 3 PRIMA study presented at ESMO last year and simultaneously published in the NEJM. Recall that the majority of women (51%) had homologous-recombination deficiency (HRD) and this subset saw the greatest benefit.

Flying high in the DDR space?

We have now seen clinical benefit in the PARP inhibitors in four tumour types driven by DNA damage repair (DDR) deficiencies, namely ovarian, breast, pancreatic, and prostate cancers.

How do we go about extending the concept of DDR in terms of the biology of other tumour types?

A number of related pathway targets have been investigated, including ATM/ATR, Chk1, Wee–1 and others, with mixed success.

It’s not the nature of oncology R&D to stand still, however; what if we could turn things on their head and think creatively about the problems still to be addressed?

One particular new company to the PARP space is doing just that… so what are they doing and what’s different about their approach?

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