Biotech Strategy Blog

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

Posts tagged ‘acquired resistance’

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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New opportunities for Menin inhibitors

Tree of Hope

Some recent research in a specific area has provided some helpful and stimulating findings, which may lead to some unexpected combination trials in the future.

We all know cancer is best beaten with combinations and regimen approaches, but a key question always remains the same no matter which company is doing the R&D – which are the best options to evaluate together given the limited time, resources, and budget available?

Even large pharmas cannot explore every single possibility.

Suppose a company has the luxury of five early stage agents either in-house or available to them in a partnership. This would give 10 potential phase 1 doublets they could evaluate. If we include triplets as an option then we can add a further 60 possibilities on top.

It might sound like a tree of hope, yet these are unrealistic scenarios because few companies will run 70 phase 1 trials just to figure out the optimal regimen to go forward with in a phase 3 study. In fact, I seriously doubt if anyone would seek to attempt this number in mice studies either!

Despite all the misgivings people have about translating preclinical data to humans with advanced cancers, we often need to be reminded to keep our feet on the ground.

It’s not a matter of alchemy where chemists and translational researchers seek the ’elixir of life,” or a pill that would cure all cancers. Instead we have to use some common sense based on what we know and how things might shake out.

In today’s post we look at what some future combinations might look like and who the key players might be…

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Novel strategies for taking on advanced cancers

Signalling intentions… Tall Ships Race 2024 Turku, Finland

It’s an unfortunate truth very few currently available cancer therapies are capable of inducing durable complete responses in people with advanced solid cancers.

This is largely due to challenges such as tumour heterogeneity and acquired resistance or immune escape.

How can we change this situation for the better?

There are only so many targets to go around and existing modalities have their limits, thus what we need is some more innovative and creative strategies.

In this post we hone in on two such examples to explore what they and how they might make a difference…

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Sorting out the clunkers in a crowded field

Early last year I started tracking and coding the various elements as new ADC agents began emerging post JPM23 from various conference presentations and BD&L activity. I quickly ran out of colours!

A couple of trends quickly became apparent.

Big Pharma – needing to replenish pipelines – were gleefully snapping up topoisomerase-based ADCs and Asian countries who had a seemingly bottomless pit to supply their pent-up demand were the main beneficiaries.

Bergen harbour – where elegant ships and rusted clunkers rub should to shoulder

There are a number of reasons why this may not be the best idea in terms of R&D, however.

Some of them may do well, while many will turn out to be clunkers and likely fail.

This latest gold rush is not going to end well for some players and there will be many tears before bed time once everything shake out.

Today’s story adds some more evidence to the mix for consideration…

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The hidden dangers of tulip mania

Dog Drug Heaven high in the hills above Edinburgh

With every new shiny or sparkly category coming through oncology pipelines, there’s nearly always a sense of fervent tulip mania once the niche reaches a certain threshold of new compounds moving into the clinic.

The latest such example is antibody-drug conjugates (ADCs).

It’s time to think about some of the practicalities and reality checks because few things in oncology R&D ought to be viewed from the perspective of rose tinted glasses.

Instead of breathless hype, we’re taking a common sense perspective deeply rooted in first principles around targeted therapies.

Look before you leap into the unknown – because there are plenty of clues regarding where this niche is headed for many early stage agents…

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AACR23 – is the Florida sun shining on KRAS?

Orlando – AACR23 is in full swing and one of the areas gaining a lot of attention at the meeting is a surfeit of new data on targeting KRAS.

In this post we review some of the key data presented so far, along with commentary from some of the education sessions we’ve covered, which not everyone may have attended.

Can we beat KRAS and, if not, what are the challenges to be overcome? How should we go about this endeavour?  Is it all sun and palm trees in Florida?

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Addressing acquired resistance through novel combination strategies

Sometimes it may seem as though the hottest – and often only things – which get attention these days are IO related, while the good old fashioned targeted therapies are ignored.

St Charles Streetcar, New Orleans LA

Do so at your peril, folks, because there’s a lot of useful data coming through these days exploring novel combination approaches to overcome acquired resistance and improve outcomes for people with various advanced cancers!

In this post, we take a look at some emerging preclinical data from the annual meeting of AACR in New Orleans, which either has led to new early stage combination trials in people with certain advanced cancers or will be starting soon.

The good news is the science is solid and the need for novel combinations in these settings is a high one – it’s time to get on board and learn about these important developments…

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An authentic and novel approach to designing novel anti-cancer drugs

A couple of years ago I was listening to an early stage drug hunter expert talk about how they were going to do things differently in building their oncology pipeline.

Simulations galore!

At the time, they had no official targets announced and much of the noise and attention was on the filling of seats on the Board or leading positions in the company, so very early days indeed.

The following year heralded an IPO, dosing of the initial patient in their inaugural clinical trial and just a few months later, their very first licensing deal and collaboration with a large Pharma company, so clearly a young biotech company going places.

What’s happened since and what so different or special about their approach to cancer drug development?

It turns out there were some surprises in store and some very cool science behind it…

BSB subscribers can learn more about our latest interview in the AI/deep learning niche – you can read all about it by logging in or click to access our ongoing oncology coverage.

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Are AI and machine learning alive or dead in oncology?

Have you ever wondered where the ideas and new molecules come from in terms of oncology drug discovery platforms?

New York, New York!

Why are young biotechs often prolific at generating novel approaches while big Pharmas are slow with a tendency to follow the crowd?

Much of the answer lies in a combination of nimbleness, focus, and flexibilty – not just in terms of fresh ideas, but also a willingness to tackle the difficult targets requiring deeper knowledge and problem solving.

In order to generate these targets and molecules, however, you need a consistent platform to test and predict how the scaffolds and targets might integrate.

Here we look at a company with a solid reputation in this space and also hihghlight how they are emerging as a biotech company in their own right with an interesting and diverse pipeline focused on a variety of different targets…

BSB subscribers can read more on our latest look at an intriguing company active in the AI and machine learning space in terms of drug discovery – you can log-in or click to access our ongoing oncology coverage.

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AACR21 Preview 6 Exploring a novel and early target for cancer therapeutics

What stands out as a possible new cancer target to therapeutically drug?

Every year as part of our AACR Preview series, I pick a novel target to illustrate where innovative ideas are coming to the fore based on new and often early scientific evidence.

There is also the hope they might lead to future clinical drug development and emerging pipelines.

Some of these targets can turn out to be tough to drug for various reasons, including narrow therapeutic windows limiting the dosing schedule that can be realistically achieved (bromodomains come to mind), while others lead to some intriguing compounds which end up going further than expected.

Here’s the sixth article in this year’s series where we identify and discuss an early novel target of interest…

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