Biotech Strategy Blog

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

Posts tagged ‘Boehringer’

T Cell Engager Comeback: Why solid tumors may finally yield

While most eyes at ASCO will be on the marquee phase 3 ADC readouts, a quieter revolution may be unfolding in the T cell engager space.

Created by Wall-E from a Blue Ice Publishing prmpt

After years of struggling to replicate hematologic successes in solid tumours – and several high-profile failures that nearly killed the field – a new generation of engineered bispecifics is finally showing signs of life.

The question is whether these sophisticated molecular machines can overcome the fundamental challenges, which have made solid tumour bispecifics such a graveyard for promising compounds.

In this latest review we take a look at some early-stage agents, some of which are looking quite encouraging while others might struggle with headwinds…

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A novel bispecific ADC to watch out for

Companies think they see gold in the distance, while ignoring the narrowing, darker hazards close by

If 2024 was the year of topoisomerase-I antibody-drug conjugates (ADCs) then 2025 is likely to herald a different series of trends within this niche.

Adding on extra payloads or targets may seem like a logical extension – as witnessed by the flurry of bispecific and dual-payload ADCs. This approach often ignores the many underlying complexities and challenges involved because these are highly complex and sophisticated agents to develop.  It’s not simply a matter of swapping out different elements akin to Lego bricks and hoping for the best.

In this article, we discuss a number of issues facing companies chasing the ADC dream, as well as an early example of an intriguing novel ADC target to pay attention to going forwards.

In the long run, the near and far might turn out to be relative, depending on your perspective…

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The Nexus Frontier

Futuristic image created with WALL-E   Source: Blue Ice Publishing

The Nexus Frontier stands as a bold and groovy movement at the intersection of discovery and understanding, where complexity meets clarity.

It’s a frontier where scientific rigour and human relatability converge.

In other words, it’s time for a collaborative guest post from a physician CMO to learn about his perspectives and reactions to recently presented data.

What jumped out?

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RevMed’s approach to kicking KRAS to the kerb

Source: Dr Tillman Pearce, CMO at ALAFIA

It’s all too easy to take life for granted until one is faced with an unexpected devastating diagnosis such as a terminal Stage IV cancer – cholangiocarcinoma or pancreatic ductal adenocarcinoma (PDAC) come to mind, for example.

When we see new early stage agents emerge from Pharma pipelines showing a promising and different concept from what’s gone before then it’s hard to imagine anyone not wanting to see it break the mould and succeed, regardless of who the company is.

This doesn’t mean we should borrow a pair of Dame Edna Everage’s sparkly rose-tinted glasses and abandon common sense.

Last Friday we saw the first-in-human data from a phase 1 readout centred on Revolution Medicines new KRAS inhibitor, RMC-9805, in a presentation by Dr David Hong at the ENA Triple meeting in Barcelona.

The company also presented several posters on the pipeline agents and held a conference call to discuss their progress and next steps.  The PanCan community are naturally excited to see some progress with the early stage agents.

This is the second example we’ve seen this month where a company has publicly announced a phase 3 trial opening based almost entirely on phase 1 data.  Will it end well or flounder down the road?

In our latest analysis we take a look at some of the many challenges and opportunities to consider when handicapping the odds of success…

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Just can’t get enough

Gone Fishing!

The dawn of the 1980s represented a much more optimistic future than what it eventually turned out to be – will we see the same trend evolve with the seemingly myriad of attempts to box in certain cancer targets?

In some ways this has turned into a bit of a fishing expedition in several ways:

  • Uncovering mechanisms of resistance
  • Finding rational combinations with a decent therapeutic window
  • Developing next generation agents to address the limitations of the earlier versions

If we want to see success in the clinic then what might this look like in the next round of trials and who are the companies active in developing them?

It turns out there are a few surprises in store…

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Wrestling an intractable cancer target into submission

Santa Fe, NM

When it comes to intractable or tricky to drug targets, I’ve always thought this is where companies should put their best people on these projects and give them space and creativity to come up with new solutions to an age old problem.

There is both beauty and opportunity in either being first or best to a previously untamed oncology niche.

Why chase the herd of me-toos when you can conquer what was previously considered impossible?

After all, this is where there is advantage to be gained, especially if you have a head start then it’s up to everyone else to define how they are different and better than the first to the frontier land.

In our latest review, we explore the fresh opportunities to be had for savvy companies who have created novel pipeline agents in an early, yet emerging niche…

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Pointing the IO way

Pointing the way

A few years ago at SITC 2016, we wrote about a raft of early agents, which were then considered all the rage against a variety targets at the time…

  • Modulating MDSCs, M2 TAMs, Tregs
  • TLR agonists
  • Adding MEK or TIGIT to checkpoint blockade
  • Immune agonists from 4-1BB to VISTA
  • And so on…

While some of the trials are still ongoing, a few have fallen by the wayside and still other targets continue to receive sporadic attention.

This year’s crop of emerging agents and targets are a very different bunch altogether and the breathless hype has been replaced by much more quiet determination and optimism.

What to watch out for in 2023? 

We offer eight areas to explore and check out – most of them are up and coming small to medium biotechs focused on oncology rather than big pharma cos with money to burn…

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Intriguing progress on the KRAS front

Tackling intractable targets and tumour escape/evasion

Understanding clonal evolution ought to be an essential part of figuring out how to tackle intractable or tricky targets such as KRAS.

Inevitably chronic treatment with monotherapy will exert selective pressure on a given tumour so it reacts by escaping and signalling elsewhere in order to ensure its continued survival.

If we add in another agent, it may work for a while and then the same thing happens again.

What if we could break out of this cycle and try some novel approaches, find more potent agents, or even rational combinations to try and box in the resistance?

In our third ASCO Preview we take a look at some of the progress being made and where things might be headed in the near to medium term future…

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AACR23 Insights on gems from the poster halls – Part 1

At AACR annual meetings there is a phenomenal number of posters on display, truly a smorgasbord of up and coming agents and targets relevant to cancer research.

I can still remember the trials and tribulations traveling from the UK to Boston as a PhD student on a limited budget to present a poster at a major US conference, so would like to congratulate all the young researchers with posters at this year’s AACR meeting. Presenting at an international meeting is a big deal and this year was the first time post-pandemic many could easily travel without restriction.

Fishing for gems in the poster halls

With several thousand posters to choose from the selection of what caught our interest is, by definition, subjective.

We’ve chosen to focus on new products in development or novel targets.

In part one of our AACR gems from the poster hall, we have 10 posters from emerging biotech companies with early stage data.

For each poster we’ve highlighted what we liked about the data, what to watch out for, and what our overall impressions were relative to some of the competition.  Not all of them will make it through to phase 3, but some could show some initial promise.

If you haven’t finished your AACR23 trip report and want a few suggestions of what you might have missed or what emerging agents could be highlighted, this post may be for you.

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AACR23 Preview 7 – Surfeit of riches

With the rapidly evolving KRAS niche from seemingly intractable therapeutically to a vast array of different MOAs now appearing in company pipelines, you could well be forgiven for thinking of Perry Como singing ‘it’s beginning to look a lot like Christmas.’ 

The sheer number of new agents, novel targets, different MOAs, and even creative combination strategies emerging is making this niche incredibly hard – albeit rewarding – to keep up with.

Every time we post even a mini update there seems to be something new to discuss and the latest review is no different in this respect… prepare to be pleasantly surprised!

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