Biotech Strategy Blog

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

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There are at seemingly endless genes associated with genomic instability and the development of cancer – there are at least 450 genes associated with DNA Damage Repair (DDR) alone, for example.

This means it is, perhaps, not at all surprising these can not only induce significant changes in various tumours, but they also might have deeper interactions between them as well, many of which we may not yet know about.

Just as we have seen some success with PARP inhibitors in patients with BRCA loss of function, so too are companies seeking to exploit additional vulnerabilities by targeting the achilles heel with other paired approaches such as ATR inhibitors in cancers where there is ATM loss of function.

There has been a raft of data in this niche from several agents in this class so it’s time to turn our attention to reviewing what we learned from the many subtleties and nuances that inevitably abound in this DDR subniche, including recent data presented by Repare Therapeutics at the AACR-NCI-EORTC meeting…

BSB subscribers can read up on our latest commentary and analysis from the cancer conference season for our ongoing TRIPLE meeting coverage – you can either log-in or click to access our latest analysis.

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Where are we headed in the KRAS niche? Who are the new emerging players?

One of the most fascinating and intense sessions at the AACR-NCI-EORTC conference this weekend centred around the KRAS niche.

I think for too long many observers have focused on only two companies developing selective inhibitors and yet it is clear we have much to do in terms of improving outcomes for the majority of patients since some will be resistant upfront and not respond at all, while others will develop resistance over time.

What then?

The good news is there is a wealth of novel approaches and also quite a few other companies active in this space, as well as next generation inhibitors also coming along.

Just as the odds-on favourite doesn’t always win the Grand National – there are drug equivalents of Becher’s Brook after all – what looked liked long shots to many a mere two years ago at TARGETS19, are now looking more encouraging.

There’s all to play for and so it’s time for us to offer some perspectives and insights on a raft of new developments in the KRAS niche…

BSB subscribers can read up on our latest commentary and analysis from the cancer conference season for our ongoing TRIPLE meeting coverage – you can log-in or click to access our latest analysis.

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O’ still small voice of calm

Later today we will see the much anticipated first look at the initial data from Relay on their selective FGFR2 inhibitor, RLY–4008. Their poster on the PI3Kα inhibitor, RLY–2608 was made available in the ePoster hall yesterday.

Ahead of the presentation in the second plenary session, we take a look at some of the issues and challenges to think about.

This is especially key since this is a first-in-human phase 1 trial, meaning the dose escalation portion of the study where the focus is on tolerability and safety, and where it also behooves us to look at the broader picture in this context rather than indulge in breathless hype.

BSB subscribers can read up on our latest commentary and analysis from the cancer conference season on our TRIPLE meeting coverage – you can log-in or click to access our latest analysis.

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It’s time to look at progress on the ADC front, something we sporadically cover where there are new phase 1 or 2 data of note.

Making waves in the ADC niche

Compared to the myriad of targeted small molecules and IO therapies out there, ADCs and related drug conjugates form a much smaller class of agents, although this is slowly changing as the technology develops on several fronts.

Yesterday’s first plenary session at the 2021 Targets/Triple meeting focused on new developments in tumour-targeted conjugates including a couple of early stage projects, which should be well worth watching out for and following over time.

It wasn’t all plain sailing, however, with plenty of important caveats and nuances to be aware of…

BSB subscribers can read up on our latest commentary and analysis from the cancer conference season on our TRIPLE meeting coverage – you can log-in or click to access our latest analysis.

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It’s time to turn our attention to the annual AACR-NCI-EORTC international conference on molecular targets and cancer therapeutics, often dubbed simply as TARGETS or TRIPLE for many industry observers.

Spotting the wood from the trees

With the ongoing pandemic, this year’s meeting remains a virtual one and runs from today through Sunday.

There’s quite a lot of intriguing abstracts to cover this year so we kick off our coverage with a look at KRAS combinations.

While the single agent activity of both sotorasib and adagrasib has been encouraging in lung cancer with G12C mutations, the rest test was always going to be what combinations will emerge as winners in terms of overcoming primary or acquired resistance (the mechanisms might be different in each case) in order to improve outcomes further.

Any agent targeting the MAPK pathway will necessarily be challenging in combination with KRAS inhibitors due to toxicities, but are there other approaches or could we finesse the dosing/schedules more optimally?

Here we look at two such combination strategies to see how they are faring…

BSB subscribers can read up on our latest commentary and analysis from the cancer conference season as we begin our TRIPLE meeting coverage – you can log-in or click to access our latest analysis.

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Up in the air

Last week and this week have been a crazy time in the cancer conference schedule…

To see what I mean, we attended the AACR specialist meeting on aggressive lymphomas (DLBCL) on Thursday and Friday, then Monday and Tuesday heralded silly o’clock (5am) starts for the 3rd Annual Crick International Cancer Conference in London, now we’re dialed into another AACR specialist event on Tumour Immunology and Immunotherapy, not to mention the Targets/TRIPLE meeting coming up later this week as well.  There were also a couple of excellent lunch time lectures thrown in to the mix as well.

It’s all systems go, Thunderbirds!

Sometimes it’s as though we’re living in a modern Third Life during the pandemic where remote events allow one to easily ‘fly’ around the globe, eagerly dropping into intriguing meetings we likely wouldn’t otherwise be able to get to in person.

The good news is one gets to learn an incredible amount from the sessions and doesn’t accidentally switch into a giant skeletal Zombie avatar (yes I did that once, much to my embarrassment), the bad news is finding the time to actually sit down, think clearly, and write up one’s chicken scratch notes to share with readers.

Before I dash off again to listen to some cool keynotes from Drs Miriam Merad and Crystal Mackall, it’s take to take a deep breath and explore some of the learnings from the Lymphoma meeting as a kind of early ASH21 Preview because there will be important readouts coming out in December…

BSB subscribers can read up on our latest commentary and analysis from the cancer conference season – you can log-in or click to access our latest analysis.

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One of the things that struck me at this year’s ESMO conference was the sheer variety and richness of the data across multiple treatment modalities, tumour types and even new products coming through the pipeline to vie with established products for time and attention.

It’s also interesting to see what kind of questions readers have – it’s time for another mailbag session where we take reader questions and attempt to put some colour and context on the answers, as well as offer some predictions in some cases.

The current crop spanned a wide range of topics and issues from TKIs and DDR agents to immunotherapy, and not just checkpoint blockade either!  People specifically wanted to know about various targets and different modalities, including cell therapies.

So what’s on offer in the candy store today and were they substantial in nature or should we dismiss them as weak sugar pills?

BSB subscribers can read up on our latest discussion and analysis from the ESMO conference – you can log-in or click to access our latest analysis.

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With regards to today’s focus on a phase 2 randomised controlled trial (RCT), it is an intriguing development to be thinking about because usually it is phase 3 trials which tend to be rather controversial and generate a lot of reader questions.  This especially true when it’s a negative study and people want to know why, or what on earth happened?!

Between the lonely sea and sky…

It’s rare for a positive phase 2 trial to lead to more questions than any other studies being presented at a given cancer conference.

I must admit this was probably my favourite data of the ESMO meeting because it offers plenty of possibilities and also broader encouragement for the field when you consider how many studies have tried to manipulate the tumour microenvironment and not succeeded.

Between the current readout and the forthcoming pivotal phase 3 trial, however, lie a number of key questions which need to be addressed, as well as plenty of subtleties and nuance to think about carefully.

So what’s in store on the lung cancer front?

BSB subscribers can read up on our latest commentary and analysis from the ESMO conference, including expert opinions and reactions – you can log-in or click to access our latest analysis.

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Early developmental therapeutics is often akin to finding Nemo or spotting the hidden nuggets in the wild

In our latest look at novel agents in Developmental Therapeutics, we discuss some of the inherent challenges many companies face when conducting phase 1 research through the lens of Syros’s progress with their early stage agent targeting both transcription and cell cycle arrest.

Finding a balance between efficacy and tolerability is often much trickier than many outside observers realise, but it can be done.

Of course, this is before we even consider which tumour types might be optimal to pursue in further trials…

BSB subscribers can read more on our latest update and commentary from the ESMO conference – you can log-in or click to access our latest analysis.

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When it comes to targeted therapies, far too many external observers do not ‘see’ beyond the pretty scenery.

There’s an old obvious yet wise fable down here in Florida, which is often applicable to early stage oncology drug development – if it looks, snaps, or waddles like an alligator, do not feed it for you will surely get bitten (badly).

In this post we take a careful look at the updated adagrasib data in colorectal cancer presented at ESMO21.

There’s a lot of nuance, subtlety and questions this trial so far has not answered, and that will need to be considered if you don’t want to run the risk of being bitten by the lurking alligators.

BSB subscribers can read more about the challenges in interpreting the adagrasib CRC data presented at this year’s ESMO congress – you can log-in or click to access our latest analysis.

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