Biotech Strategy Blog

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

Posts tagged ‘PARP7’

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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A saying for the ages from Albert Einstein

Oncology R&D is – perhaps surprisingly – very much like the bicycle analogy Albert Einstein described.

There are many ways we can see this happening at meetings such as AACR and ASCO as companies struggle to finesse the therapeutic window and balance efficacy with toxicity, for example.

Or how about finding creative ways to extend and broaden a particular drug class?

Another approach might be to take an entirely different angle to tackling a tumour type by targeting an antigen few others are pursuing. Just because the herd is going in one direction doesn’t mean you should follow them down the same path as well.

Then there’s switching modalities, orthosteric versus allosteric inhibitors, or how about some med chem magic where researchers seek to enhance the good properties and minimise the weaknesses while still hitting a target selectively?

All of these methods require some kind of balancing act if you want your pipeline to move forward rather remain still or fall over in the doldrums.

Today’s post has all of this and more – there are some novel compounds and targets, emerging biotechs and big pharmas, as well as innovative thinking to make a difference. Several of these agents are first-in-class, which means the rest of us can learn much from the lessons they have shared.

What’s not to like?

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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…

To learn more from our oncology analysis and get a heads up on insights and commentary emerging from the annual AACR meeting subscribers can log-in or you can click to gain access to BSB Premium Content.

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