Biotech Strategy Blog

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

Posts tagged ‘TIGIT’

Making sense of all the TIGIT data at ASCO23

Graffiti in Adams Morgan, Chicago

Continuing our coverage of the annual meeting of ASCO in Chicago I felt compelled to review the actual data presented at the meeting.

Regardless of whether you are bullish or bearish about the target – or even specific agents in the niche – there are some important subtleties and nuances to be aware of and take into consideration.

Here we offer a detailed look at key issues to think about in the broader context of new product development and early stage clinical trials…

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On TIGIT, ADCs, and other stories

Some ASCO23 abstracts to grab your attention!

As we head into the annual meeting of the American Society of Clinical Oncology (ASCO), it’s time to review some key abstracts which may grab your attention.

Of course not all of these will be positive in nature, yet some are already planned for phase 3 investigation on the basis of some rather skimpy early data…

While at the other end of the extreme are some important data largely under many people’s radar.

Here we highlight a dozen examples of what’s coming this weekend, explain what to watch out for and offer some important caveats or questions to think about.

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Tipping the TIGIT balance

Are we experiencing a sunrise or sunset for TIGIT?

TIGIT has certainly generated significant positive and negative reactions over the last few years, as it wenders its way through the Gartner hype cycle.

Sometimes people think things are much more clear cut than they actually are in practice; the complex TIGIT pathway is a great example of this fallacy.

With targeted therapies we have consistently seen the emergence of acquired resistance over time – a similar phenomenon happens with immunotherapies too as the tumour adapts in response to selective pressure.  These changes can lead to immune evasion, which means less tumour cells are being killed, leading to relapse.

We haven’t seen much data on what the mechanisms of resistance are, in part because the anti-TIGIT trials are starting to read out and it takes time to figure out what’s happening.

There’s some new data from academia to consider, which may shine a light on one potential solution as well as offering an opportunity for another NewCo to rise.

Here’s a look at the science behind the story…

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Emerging biotechs and novel IO concepts to watch out for

There are plenty of innovative and creative ideas coming to the fore in oncology R&D of late, many of which are quite different twists on what we currently have available.

Early oncology development is rarely plain sailing – some fly like the wind, others fall over

As Dr Dan Chen of Engenuity noted in his talk in the SITC22 preconference session on lessons learned from IO combinations, if we want to cut to the chase when looking at emerging agents then we need to ask ourselves whether any of the concepts are seeking to address the limitations of the current products, particularly those associated with either primary or secondary immune escape.

After all, repeating the same old, same old is probably not going to move the needle in any meaningful way.

In thinking about which biotechs to pick for the annual SITC review, I also asked myself a couple of additional provocative questions – how are they distinguished from the competition, and in what way are they particularly compelling?

We’ll discuss these as we go through the selections, which includes both some solid developments as well as others we ought to be much more wary of offering too much hype over hope…

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SITC Preview 2 – a look at novel and emerging IO targets

After a couple of years in the doldrums with a bunch of negative phase 3 readouts, I thought this was a good opportunity to sit back and reflect on the next tranche of targets and see what we can learn about them.

The answers were quite surprising when you look at the group as a whole because not everything is about the PD(L)1 – CTLA4 axis, thank goodness.

In the latest preview we explore five different categories and highlight mostly early and novel developments coming along from early stage biotech companies, which may be of interest to our eager readers..

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What do the Konami code and targeting KRAS have in common?

It seems astonishing to realise only a couple of years ago KRAS was considered undruggable intractable and here we are, not only with one drug approved, another filed and veritable long list of fast followers, but a whole ecosystem of different agents vying for a place at the table.

The wonderful news is we are starting to think more broadly about life beyond G12C mutations, not only with different combinatorial approaches, but also also in the context of how to tackle other related mutations as well.

Here, we wanted to explore the evolving universe more broadly and assess criticality as well as applicability – which agents might shine tomorrow if clinical data turn out positive?  The simple answer is more than you know.

So just who are the rising stars in this emerging landscape and what can we learn about them?

Be warned in advance – this is one of our longest and most comprehensive reviews on BSB with over 30 compounds highlighted in different guises, so grab a cup of Joe and be prepared to come with an open mind…

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An alternative perspective on TIGIT

We’ve written a lot on TIGIT as a cancer target going back to 2015 (see examples here) as we have followed the trials and tribulations of numerous developments in this niche longitudinally.

I’ve often wondered how people would have viewed results from anti-CTLA4 trials had anti-PD(L)1 therapies came first and not the other way around.  You just imagine the disappointment this might have induced given the way things panned out!

Not all anti-PD(L)1 agents have consistently demonstrated similar results – some have succeeded where others failed. Whether this was due to differences in trial designs, different patient populations, or other factors is often something of a mystery since there is still much we don’t know – the unknown unknowns – and how they can impact performance. If they are not accounted for in the baseline characteristics then differences in outcomes might well unwittingly be impacted from the get-go.

It was always going to be tough to add in another immunotherapy agent and shift the survival curves up and to the right, thereby impacting outcomes even further.

Should we be considering the recent top line tiragolumab readouts an indication of failed trials or something else?

In our latest analysis, we consider a number of pertinent factors and discuss how they can impact performance…

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Seeing the wood from the trees in early stage oncology pipelines

One of the many challenges in the oncology space is seeing the bigger picture of how companies evolve their early stage pipelines.

For some, it’s a bit like taking a walk in the forest and not being able to see the wood from the trees – the targets chosen are rarely random, especially those involving collaborations.  There’s a reason for pursuing a given approach, particularly i it is intended to be employed in combination with an existing, approved therapy.

There are many choices out there and even those with the deepest pockets can’t have everything, so often I’m fascinated by the selections that are taken and how they might fit in.

In our latest company review, we talked to a big pharma company active in the immunotherapy niche and sought to explore the early stage agents they are developing in the context of future doublet and triplet combinations.

Why are they doing what they’re doing and how might their approach be differentiated from others?

To find out more, check out our latest expert interview, which has a few surprises in store…

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The spectre of MetMAB rises again!

A long and lonely road to nowhere ahead for TIGIT?

This morning Genentech/Roche dropped a press release providing the dreaded ‘update on’ the much anticipated interim results from SKYSCRAPER–01 phase 3 trial.

When you see language such as this, you know before you open the release the outcome will more than likely be a negative one.

Unfortunately, 2022 has already been a long year of doom and gloom for oncology trial readouts and we’re still only in May.

In our latest in-depth review we discuss what can we learn from the latest findings and how might this result impact the broader TIGIT niche?

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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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