Biotech Strategy Blog

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

Posts tagged ‘Novartis’

Voodoo in NOLA? Say it ain’t so!

A few years ago long before the advent of the KRASG12C inhibitors, a scientist once drolly stated to me that trying to drug RAS, and KRAS in particular, was akin to the med-chemist’s version of voodoo. Hah!

Fast forward a few years to AACR in New Orleans and we have a veritable feast of RAS targeted agents now coming through quite a few company pipelines in all shapes and forms from covalent and non-covalent inhibitors to molecular glues, and even bifunctional degraders.

Some voodoo, man.

In this review, we look carefully at three different companies (including biotechs and big pharma) who are actively developing various inhibitors in the RAS niche with early stage developments and look at what’s coming along behind Amgen and Mirati… the first isn’t always the best in the long run, so what should we be looking at and learning from in the next tranche?

BSB subscribers can read our latest conference coverage from AACR plus commentary and analysis – you can either log-in or click to access.

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Opening the door on our AACR22 coverage

Yes, it’s that time of the year already…

In our first Preview from the AACR annual meeting coming up next month, we’re going to highlight a couple of key topics of interest to many of our readers and also offer some context for where the selected fields are currently at and just as importantly, where they are likely headed.

The abstracts haven’t dropped yet – the regular abstract titles, authors, and text will be released tomorrow (March 8th) at 4:30 pm ET – although based on our knowledge of the field, recently published data, or presentations already rolling out we can put a good picture together of what’s what and where things are at…

BSB subscribers can read our latest commentary – you can either log-in or click to access.

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Proof that the sun came on a Wednesday in England this winter – hard not to be upbeat on days like this!!

As we continue our journey looking forward in 2022 and beyond, it’s time to start putting some meat on the bones, so to speak, in terms of what specifically we can look forward to hearing more about.

January brings a renewed sense of hope, despite the dreary weather in many places around the world, even in the Blighty the sun sometimes shines (right).

With this uplifting comes a fresh sense of new directions too, which is as true for both life in general as it is for oncology R&D.

With this in mind, in our latest review, we highlight six key areas to watch out for and explain why we are interested in following them with regards to early oncology new product development…

BSB subscribers can read up on our ongoing commentary and analysis on oncology new product development – you can either log-in or click to access the back story behind the latest innovations!

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Next generation CAR-T cell products are likely to be all the rage soon as companies seek enhanced performance of their agents, not just in terms of safety and manufacturing times, but also with regards to long term outcomes for people with various hematologic malignancies.

The various changes being made are not the same since companies in this niche all seek an edge by evaluating different strategies.

Time to wave the flag on traditional CARs and move onto next gen products?

In part one of this mini-series, we explored some of the improvements being investigated with allogeneic CAR-T cell therapy and now it’s the turn of autologous approaches to be put in the spotlight.

It’s easy to think faster manufacturing is all the rage in order to compete with off-the shelf products whether CARs or T cell engagers, but actually the changes being implemented are much more extensive and wide ranging than this.

Here, we turn our attention and offer an in depth look at what’s behind these novel developments and why they matter through the lens of not only the data presented at ASH, but also an expert interview…

BSB subscribers can read up on our ongoing commentary and analysis from the ASH annual meeting – you can either log-in or click to access the back story behind the latest innovations.

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Is the ride going to be a thrilling long or disappointingly short one?

The KRAS niche continues to rattle on at an incredible pace with new findings, new trials, or even a new molecular entity (NME) coming along seemingly every month.

In this latest update on the landscape, we discuss some important new findings, as well as a novel agent to thing about in this space, which is quite different from what we have seen before.

To be clear – this doesn’t mean a novel approach doesn’t have any legs, nor that the latest science behind where we should be going with combinations is doomed.  Indeed, sometimes finding a balance is a bit akin to a highwire act.

The important thing is to focus on the learnings and determine where the field might be headed…

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

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Source: AlphaFold

Our latest post discusses key topics around the novel target shown on the right – brownie points to anyone who can guess which one it is!

Aside from having a lot of fun exploring protein targets with DeepMind’s AlphaFold tool, they also help illustrate something important, which is the degree of confidence around the various aspects from dark blue for high confidence and yellow for very low confidence predictions.

Tau, if you haven’t yet seen it, is truly a hot mess compared to today’s choice!

While there is always the concern about whether a particular protein is a marker or a valid oncogene target, we have to start somewhere and see where the clinical trials take us because some modalities might turn out to be much better ways of approaching the problem of ‘druggability’ than others.

I went into this foray with an open mind and some degree of hope because let’s face it, we need more new agents against novel targets than we do of yet more me-toos against old targets…

BSB subscribers can read more on our latest update regarding a novel early stage pipeline target – you can log-in or click to access our latest content.

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A decade ago Novartis and Genentech/Roche were all the rage in oncology with their small molecule, CAR-T cell therapies, and a myriad of antibody programs seemingly in the news every month then things went quiet as agents either successfully made it to market, or were dutifully dispatched to dog drug heaven.

In the meantime, other companies and various novel targets came to the fore such as various next generation agents in lung cancer, bispecific T cell engagers, KRAS inhibitors, and such like, while different companies and targets took on a new focus.

This doesn’t mean the big two aren’t active, more that they are replenishing and moving earlier compounds along and these can take a while to move through discovery and preclinical to phase 1 trials.  The bridge across the two is always kept busy in large pharmas, in both directions.

With this in mind, I was keen to catch up with Novartis to discuss their new early stage pipeline.  It’s both broad and deep, as you might expect, but what stands out and what’s something new to watch out for?

BSB subscribers can read more on our latest update regarding SHP2 and RAS addicted cancers as well as other early stage pipeline targets – you can log-in or click to access our latest expert interview.

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Degron (red)  Credit: Dmeyer314 via wikipedia

One of the emerging hot areas in cancer research these days is the field of protein degradation, which finally seems to have come of age.

This also means plenty of opportunities to discuss new developments as they evolve.

So what’s new and why are the latest updates important?

BSB subscribers can read more on our latest look at targeted protein degradation related topics – you can log-in or click to access our ongoing oncology coverage.

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ASCO21 – we may not be in Chicago, but this year’s virtual ASCO annual meeting does not disappoint in terms of a series of important clinical data emerging, which have the potential to change the cancer treatment landscape.

The results of the Novartis sponsored VISION trial with 177Lu-PSMA–617 in metastatic castration resistant prostate cancer (mCRPC) being presented in Sunday’s plenary session opens the door to a new line of treatment options which can only be of benefit to men with refractory disease.

Whether 177Lu-PSMA–617 will end up being the best radioligand therapy targeting PSMA (Prostate Specific Membrane Antigen) remains to be seen, but the company are to be congratulated in breaking new ground, with a clear path to market strategy enabling them to be the first to market in this indication.

Radioligand therapy combines a radioisotope that causes DNA damage, leading to replication stress or cell death with a tumour targeting compound. It offers a lot of potential in many cancer disease settings and is a topic we expect to hear more about as other companies follow Novartis’ lead and more knowledge is gained about optimal patient selection, dosing, sequencing and combination strategies.

Is it Mardi Gras time at ASCO?

For an expert perspective on what the VISION trial means in the context of the evolving prostate cancer landscape, BSB spoke with Dr Oliver Sartor (Tulane), who participated in the 177Lu-PSMA–617 trial.

Dr Oliver Sartor is a global prostate cancer expert who we’ve had the pleasure to talk with a few times over the years. He’s a professor at Tulane University in New Orleans and Medical Director of the Tulane Cancer Center.

He cheerfully told BSB:

“This is an exciting development with the VISION trial and I think it changes the landscape, even though it is sort of at the end of therapy – these patients were pretty heavily pre-treated.

I think it has implications as we look over the overall landscape for a whole variety of patients, and of course, this therapy is likely to move earlier and trials are already designed to help it move earlier. So I’m excited about the progress for a PSMA targeted therapy with Lutetium–177 and I think it is going to have implications for years to come.

BSB subscribers can read more of Dr Sartor’s perspective on the VISION trial and emerging prostate cancer landscape, subscribers can log-in or you can click to read our ASCO21 coverage.

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We have been following the progress of small molecule inhibitors targeting the menin-chromatin interaction which leads to NPM1 mutated or MLL-rearranged acute leukemias for over a year now.

In the beginning there was Syndax and Kura Oncology, now there’s a growing list of other companies entering this niche, both big and small.

In this post we take a look at what’s new in the landscape and also explore Syndax’s updated phase 1 data announced this morning.

Where are things headed and what can we learn about the latest data drop?

To learn more about the Menin NPM1-MLLr niche and get a heads up on our oncology commentary and insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

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