Biotech Strategy Blog

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

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5 important topics to watch out for at AACR22 on bispecifics

In the first part of our bispecific antibody review from the AACR front (the second will post next week), we highlight some strategic issues of interest to the field through the lens of several company’s data being presented at the meeting.

When we look at the themes of the meeting (right) we learn about the focus for this year’s event:

  • Decoding cancer complexity
  • Integrating science
  • Transforming patient outcomes

These are all particularly relevant to the the bispecific niche because whilst there are many of them, not all will make it to the finish line if they fail to improve outcomes and some will be consigned to the dreaded dog drug heaven status.

Think about it – you can have the grooviest bispecific molecule design ever, but if people taking it don’t live longer then it will likely get canned down the road in order to make way for a new era of novel targets and agents.

It’s time for some weekend reading – in the first part of our look at the bispecific antibody space, we highlight five key elements (with examples) to watch out for…

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The paradox of immune cell populations and transcription factors

It’s interesting to me how people often think of science as absolutes or black and white, and yet paradoxically we consistently see more yin and yang effects, with the tipping point determined by context or the specific situations encountered.

In immunology, there’s also a fine line between too much and too little thus finding the threshold is a very tricky thing indeed.

For a long time I have been fascinated by what I call the hidden underbelly in immunology… we look at various inhibitory or stimulatory factors in response to a particular targeted therapy all the while ignoring the vast networks of transcription factors, which might offer some helpful context to any particular situation.

Often times, companies rush headlong into clinical trials without really paying attention to these details, some of which may exert effects not considered in the bigger picture and end up being surprised or blindsided down the road.

Here then, we explore some important recent research, which may well open quite a few people’s eyes and reconsider when is enough, enough – or even too much – and how does this line have a role to play in the immuno-oncology (IO) field?

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The battle for early stage lung cancer continues apace

Sunrise or sunset in NSCLC?

Is it time for the dawn of a new era in early stage lung cancer or are the initial trials more of a sunset on future opportunities due to more modest than expected data?

One challenge with interim readouts in the adjuvant setting is they are a reflection of the top part of a very long survival curve, so large differences are rarely apparent at this stage when the timeline might be going out 10-12 years.  This is especially true for IO studies where these agents have consistently shown to impact landmark survival and the long tail of the Kaplan-Meier curves.

While previous studies more than a decade ago have shown some benefit for chemotherapy over observation in terms of overall survival, we have no other reference points in lung cancer, unlike breast and colon trials where some targeted therapies have seen success in the adjuvant setting.

This is very much a case then of ‘once more unto the breach, dear friends,’ as Shakespeare would say.

We have already seen approvals for immunotherapies in both neoadjuvant (nivolumab) and adjuvant (durvalumab and atezolizumab) stages of lung cancer, now it’s time to put pembrolizumab in the spotlight…

Are they building a cathedral or a brick wall?

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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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New directions and opportunities with intractable oncology targets

All aboard for some new directions in oncology new product development!

This is one of those posts where we may have to re-jig the title as ‘New directions against formerly intractable oncology targets’ – if all goes well in the clinic.

In past years at AACR, we have written a series of different previews ahead of the meeting highlighting key areas of oncology new product development.

They might include different targets, modalities, targeted or immunotherapies, emerging science, what’s new in basic or translational science, biomarkers of interest and so on.

At least one of the series will explore an early novel target of interest, which is the focus of today’s post.  It includes research from academia, big pharma and small biotechs in a thriving and evolving niche with a mix of inhibitors and degraders.

This is also an area which rarely receives much attention, probably because it’s too early for many observers and the science isn’t particularly easy to understand either.

In this review, we’ve attempted to summarise and condense some of the main emerging themes around this particular target with a look at what are the potential keys to success, where companies are at with their pipelines, and importantly, what to watch out for at AACR next month…

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Challenges and opportunities with two different onco modalities

Paris, 2022

With the AACR annual meeting coming up next month, it seemed a good opportunity to highlight some relevant findings from another cancer conference held this week (ESMO Targeted Anticancer Therapies congress or TAT for short) as a warm-up for the bigger event since there is some handy overlap topic wise.

Having very recently been in Paris (TAT changed to a virtual only meeting), I can say it didn’t feel very spring-like at all (right), quite the opposite!

Europe continues under a cloud at the moment with the Ukraine war very much to the fore – European Lung has also been moved to a virtual event as the conference venue in Prague is quite rightly being converted into a refugee assistance centre.

Despite all the prevailing gloom, there were quite a few important nuggets of interest to share from TAT this year…

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AACR22 Preview 1 – Key topics to watch out for

Opening the door on our AACR22 coverage

Yes, it’s that time of the year already…

In our first Preview from the AACR annual meeting coming up next month, we’re going to highlight a couple of key topics of interest to many of our readers and also offer some context for where the selected fields are currently at and just as importantly, where they are likely headed.

The abstracts haven’t dropped yet – the regular abstract titles, authors, and text will be released tomorrow (March 8th) at 4:30 pm ET – although based on our knowledge of the field, recently published data, or presentations already rolling out we can put a good picture together of what’s what and where things are at…

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Aspiring to new heights – and new modalities

With several important conferences coming up over the next 4-6 weeks, this is a good time to focus on an emerging modality.

This is an area which is slowly starting to see more interest from various biotech and pharma companies and yet the number of permuations and formats involved to optimise performance may well stymy rapid progress.

The big question I think for many of us is will they add to and go beyond what we have already or will they simply be another way of doing the same thing?

In this latest review of some important data we explore what’s what and what’s not in the context of the current and emerging landscape…

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Through the keyhole look at an emerging area of drug development

Every now and then one comes across a scientific paper detailing a novel approach, which leads to a resurgence of interest and endeavours from the field at large.

A time when you sit, eagerly read the prose carefully and think, ‘Wow, just wow!’

This is one of those such quiet groundbreaking moments… and the future impact may well be more far reaching in oncology than many first realise.

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To degrade or inhibit, that’s the question

Continuing our coverage of the targeted protein degradation niche, we take an in-depth look at the updated clinical data on bavdegalutamide and put the initial findings in some context.

While it’s always fun to write about the early science and preclinical data, the proof of the pudding ultimately comes from the clinical trials and whether a novel agent can impact people with cancer in positive ways such that they feel better and live longer.

In this latest example, we look at what’s happening in advanced prostate cancer, an area where we are seeing a new renaissance with a variety of therapies being tested…

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