Biotech Strategy Blog

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

Posts tagged ‘Merck’

What happens when an intractable target becomes druggable-ish

A fish eye view of the market

In the third of our Preview series from this year’s AACR meeting, we’re taking a look at an early, if rapidly evolving competitive landscape involving several different modalities – proving there’s often more than one way to skin a cat drug a particular target!

When we last covered this topic there were barely half a dozen developments to highlight, since then this niche has rapidly exploded with a variety of molecules and different companies to add to the mix.

Some key questions facing this field include how will we move on from dose escalation studies, what combinations will make sound sense, and which modalities might offer a wider therapeutic window in order to be combinable with other approaches?  People will always have favourites, so we took an unbiased look at the state of play.

It’s never as easy as it first appears…

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Kicking ADCs up a notch

Orchid at Vizcaya Museum in Miami – always thought they looked like chemical structures showing us the gaps!

We highlighted a number of different types of antibody drug conjugates (ADCs) recently – yes, there’s much more to this category than simply dropping a chemo cargo on cancer cells!

In this review, we explore one of those flexible functionalities in more depth.

The cool thing about having an antibody base is creative chemists can bolt different things onto them, depending on what their goal is.

There are some really cool technology ideas being explored in research right now, which may improve not only what we can do with ADCs but also another modality.

If we think of the ADC as a modern day Trojan Horse to hide or mask the real payload in some way, the possibilities become limited only by our imagination.

The good news is there’s more than one example of this new genre to explore…

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A oncology biotech to pay attention to

We are still on a quest – a patient journey, if you like – to find new agents capable of addressing the inherent issue of why do some patient’s tumours lack immune infiltrate and how do we go about fixing it?

Chihuly Glass sculptures always remind me of upregulating MHC

Over the last decade on BSB we have explored a veritable telephone directory of immune agonists, cancer vaccines, cytokines, bispecific and trispecific antibodies, additional inhibitory checkpoints, oncolytic viruses, small molecules, chemotherapy, CAR-T cell therapies, and various others.

Few have got the job well done in advanced solid tumours. Once MHC is downregulated, it becomes much harder to generate an immune response.

Stop and think about this for a moment.

It’s been a long slog to find the next big thing and a frustrating one at that for cancer researchers slaving away at the coal face. A lot of promising agents have come and gone – some quietly, others loudly – to end up in what Dr Patricia LoRosso wittily described as ‘dog drug heaven’. It is also dispiriting to write about so many ending in failure.

The good news is there are some new signs of life coming through, although it’s too early to declare a spring rennaisance. Over the next couple of weeks we’re going to highlight a number of young biotechs with encouraging or fresh ideas being explored in the clinic.

I also don’t want to raise too many hopes – especially as I have long been sceptical about some approaches with all their breathless hype – but here’s something to keep an eye on with an open mind because if it holds up where others failed then the company could be on to something…

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Thinking outside the box

I’ve heard quite a few people frequently exclaim of late how “ADCs are hot!” Alrighty then, yet this is really only the end of the beginning because old hands know they have actually been around for quite a while.

If one was cynically minded then there’s an obvious reason – chemotherapies are usually generic these days, while ADCs bring in much higher ticket prices.

They won’t all succeed though – we’ve already seen a steadily growing graveyard of failures, which started out promising on paper then unfortunately flopped in the clinic.  Just because an area is suddenly declared hot (again) doesn’t guarantee success because these are complex molecules to design compared to small molecules with a lot of factors impinging on their performance.

What many observers have missed, however, is the deeper and broader opportunities offered beyond the often plain vanilla examples.

This is because the modality has greater flexibility than chemotherapies – you can design them such that other things can be bolted on or even hidden, Trojan horse style.

In other words, what we are seeing is an early trend with few enlightened companies starting to ‘think outside the box’ in this niche.

In the near to medium future we will see a greater volume of clinical data on these emerging approaches, which could lead to improved outcomes and longer lives for people living with cancer.

So what are these new fangled things, how do they work, and which companies are active in the futuristic ADC markets?

In this review we highlight half a dozen emerging areas around ADC technology with examples of products and companies active in these niches…

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Key oncology take aways and insights from Days 1 and 2 at JPM24

All aboard the San Francisco Milan Trolley!

With a number of oncology companies facing substantial loss of exclusivity (LOE) over the next five year strategic review period, we look at who’s at risk, how are they making up the gaps, how convincing are their arguments?  Will the flurry of acquisitions and collaborations announced over the last few months and even days make a difference?

In this series of quick reviews we offer our take aways and insights on what’s happening and whether or not they stand up to scrutiny.

Spoiler alert: some do, others do not!

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You can’t put the genie back in the bottle

Are dark clouds rolling in on TIGIT?

Often times we see a press release for a negative trial – defined here as one which missed its primary endpoint – where the overwhelming temptation is to simply announce the top level findings and be done with it.

I will argue there are valuable lessons to be learned in the process, and sometimes, perhaps realise a different trial design or selection criteria might have led to an entirely different result.

Here is one example I’d like to highlight because phase 3 trials are already underway and there may be insights we can learn from and handicap future larger trial readouts…

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Insights on an emerging competitor landscape

It’s Thanksgiving week in the US!

It’s a short week for us here on BSB because it’s Thanksgiving on Thursday followed by Black Friday the next day.

Now to be clear, we’re not having a sale on that day or even on Cyber Monday, but since it’s my birthday tomorrow, we do have a very rare offer (now live) for interested parties.

Check out our pricing page for more details!

Not all of the best drugs are born in the USA, however, as our latest landscape review and ASH23 Preview amply illustrates.

This emerging niche may have a few surprises hidden in it, and not necessarily from the expected quarters.

Here we highlight some abstracts to watch out for in San Diego in the context of recent developments in the space.

We also explain select ones we find intriguing, highlight emerging biotechs to watch out for (and why), plus identify those which could lead to some unexpected future dog drug heaven exits…

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Process is power

If you had to name one company who have executed well in the IO space, it’s hard to argue against Merck with their consistent and relentless efforts from the pembrolizumab clinical development program building a blockbuster niche by niche.

Dawn of a new IO era at ESMO23?

Beyond checkpoint blockade, what’s next?

Are they a sparkly one-horse wonder or are there real possibilities to build a kingdom based on rational combinations?

Not every phase 1 pipeline agent is going to make it to the next stage, never mind over the finish line to market – some folks might think of this as the funnel of shame. The indiscriminate mud flinging which follows an ‘as many shots on goal as possible’ winner takes-all-approach is limiting, however, when you realise it creates an achilles heel in strategic thinking.

Instead suppose you can build a linchpin to enable you to build on while offering a helping hand up to some of your other early products in combination? To do this you need optimised agents which play well when combined. Now you have a very different proposition while raising the bar to other competitors – who may not have similar agents with optimal properties.

In our latest company interview, we explore the progress with several of Merck’s early stage products, look from the lens of how they see them, and where they’re headed…

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The ADC merry-go-round

Unedited, unfiltered – the ‘hey, look at me!’ pink elephant really was this lurid!

It’s time for our second Preview from the World Congress in Lung Cancer being presented in Singapore next month.

In this edition we’re going to focus on the next raft of antibody drug conjugates (ADCs) coming through in early development.

Do any stand out as the next big kahuna or are the numbers too glaringly garish, waiting to be knocked off their coconut shies?

In this review we review the evidence and take some stands…

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AACR23 Preview 5 – an emerging landscape

Bridge over troubled waters or time to lay down?

In our latest preview, we’re taking a look at a pathway previously thought to be ‘undruggable’ – an awful term we increasingly should think carefully about using given it may only reflect the limitations of current science.

As we’ve seen with KRAS – and this piece is not about that pathway – innovative science can quickly turn the ‘undruggable’ into something much more ‘tractable’ with the right agents.

In our latest post we’re looking at the emerging landscape for a class of new agents in early development we expect to hear more about at the AACR23 annual meeting in Orlando.

Which companies will be the winners and losers is too early to tell, but much like crossing the bridge in Iwakuni, are you better off staying with the group, or taking an entirely different route to success?

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