Biotech Strategy Blog

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

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Posts by MaverickNY

A lysing kind of winter

If we want to understand where the next generation of products are coming from we have to dive deep beyond the obvious to ‘see’ where the field is going and why.

Sometimes this might involve clever strategies for hiding or masking the ability of the killer cells to ‘see’ normal cells in order to reduce on-target/off-tumour toxicities, other times we may need to use creative synthetic enhancements to give the product more robust performance in some other shape or form.

How should we go about achieving this next stage of nirvana? Can it be done, and if so, how, where, and what’s involved?

In this latest post, we take a look at what lies beyond and explain why some of the emerging ideas with cool targets might either make it through or fall at the cell therapy equivalent of Becher’s Brook at the Aintree Grand National…

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New progress in tackling intractable cancer targets

125th St subway in Harlem

It’s all too easy to think of New Jersey as the behemoth of Pharmaland in the north east, while biology dominates in nearby Boston and Cambridge, yet Manhattan is rapidly turning out to be a nice home for quite a few young biotechs with a ready made source of talent and technology.

We’ve covered several of these companies over the last couple of years, including Volastra Therapeutics in Harlem.

What’s more, they’re working on a pipeline focused on chromosomal instability (CIN).

While many companies are getting into replication stress and synthetic lethality, CIN is a specific niche referring to genomic instability where chromosomes become unstable, such that either whole chromosomes or parts of chromosomes are duplicated or deleted (aneuploidy) such as point mutations or chromosome rearrangements.

Much of the genetic heterogeneity we see in tumours is largely due to chromosomal instability.

One of the up and coming areas in cancer research is CIN and the impacts of these changes and we may be able to address them with therapeutic interventions.

We’ve been following the progress of Volastra for a couple of years now so with their latest news centred around an in-licensing deal and closing on Series A financing, this is an excellent opportunity to provide an update and discuss what these developments mean in context…

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Dark Knight Rising

Rotterdam harbour

In the latest installment of our CAR-T cell mini-series, we take a look on the ‘dark side’ as we switch from liquid to solid tumours.

We have made some great progress in leukemia, lymphomas, and even multiple myeloma while solid tumours have presented a much greater challenge for the field.

There have been some helpful developments over the last few years relevant to this front, however, although when each is seen in isolation, the potential may not be apparent.

Here we look at the bigger picture and highlight important areas, which could lead to some surprising new developments emerging over the next few years…

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Changing of the guard

A frequent challenge in oncology R&D is the fast paced nature of pipeline development such that there’s always something cool or new coming along nipping at the heels of those further ahead in clinical development coupled with the changing of the broader landscape before you even get to market.

What this means is companies with agents in phase 2 development can frequently feel rather squeezed between the two extremes.

This can lead to a lot of pondering on whether they will have enough innovation to make an impact on whatever are the favoured approaches by the time they might get to market, while at the same time offering sufficient protection against the novel compounds coming along behind.  Obviously no one drug is perfect and each will have their own achilles heels, to add to the mix and uncertainty.

For some time now there hasn’t been much in the form of new approaches in prostate cancer beyond the myriad of androgen receptor antagonists in various treatment niches plus the PARP inhibitors in a select population of men with BRCA mutations… what then?

A big question targeted therapies often have to address is their impressive initial response rates and PFS based on RECIST measurements don’t always translate into people living longer, as measured by overall survival.  No drug is without toxicities either, which means these need to be factored into the final clinical decision making and can make or break early uptake more than initially realised.

In our latest review we highlight some examples of where the field might be headed next (or not), based on some new preclinical and clinical data presented…

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The near term future in CAR-T cells is a’changing!

It’s hard to imagine It’s now almost a decade on since eagerly reading the seminal CRISPR papers from the Doudna/Charpentier and Zhang labs in Science, but what a ride it’s been!

The cool thing here is we’re now getting closer to seeing clinical grade oncology products using base editing, a next generation approach with greater precision in terms of the cuts achieved.

This technology has important implications, not only for novel CAR-T cell therapy developments (which we will be covering in more detail going forward), but also other diseases where base pair changes are necessary to address the underlying root cause of the disease.

In our latest expert interview, we caught up with the CEO of one of the ompanies active in this space for a fun science discussion about the potential implications for new product development in a variety of key topics….

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The CAR-T cell beat goes on

The first day of the 5th annual CAR- T cell meeting in Rotterdam turned out to be rather interesting indeed with a number of key presentations highlighting novel developments across a range of hematologic malignancies.

If we want to see some progress then we need to start developing new constructs with other targets beyond CD19 and CD20, which are applicable to B cell malignancies, CD123 and CD33 in AML, and BCMA in multiple myeloma.

By the way, sometimes gene edited allogeneic products might make sound scientific sense in the context of the disease being studied, but getting these through the various regulatory hoops and hurdles isn’t as easy as some might think.

Necessity is often the mother of invention requiring alternative strategies to creatively address the underlying challenges.

Here we highlight some of these developments and put them in a broader context of the evolving CAR-T cell therapy field…

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An unexpected renaissance

Rotterdam, Feb 2023

With so much focus on T cell fitness and exhaustion of late I wanted to highlight an area in the CAR-T cell space, which was all the rage a decade ago then quietly fizzled somewhat, leading many observers to wonder if it was great in theory, but not so much in practice.

This subniche is going through a renaissance of sorts as more research is conducted and we learn enough from the experiments and past mistakes to start moving forward again.

In this post, we’re gimng to focus exclusively on one of these aspects and see what’s new and where things might be headed because this isn’t an isolated incident…

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New directions in lymphomas

The landscape in various lymphoma subsets has changed in ways many may not have expected a decade or so ago and will continue to evolve further as new treatments against novel targets start to show their true colours.

Let’s not forget the original emergence of BTK inhibition caught a lot of people by surprise, so if we think about the next five years ahead, where might some of the next innovations come from and how might different segments potentially look in terms of new regimens?

In our latest expert interview, we take a look at an emerging pipeline in this hematologic niche and discuss where some of the early stage data might lead us to going forward.

Of course the caveat in oncology is most products will not actually make it to phase 3 development or even succeed there, yet the big attraction is in exploring emerging products to see where the trends might lead, because you never know which ones will shine down the road…

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Will targeting KRAS G12D prove more successful than G12C?

Are scientists and observers taking a distorted fish eye view of the KRAS world?

I’ve often wondered if in putting so much focus on ripping the progress of the G12C inhibitors to shreds, people simply lose focus of the progress being made elsewhere especially with different, yet related targets.

Here we offer some emerging highlights on several fronts, some of which ought to be well worth watching out for and others perhaps not so much…

Curious to learn more?

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Cracking the code to the MYC oncogene

Sunrise or sunset for therapeutics against an intractable oncogene?

In our perpetual search for cool and interesting new developments coming through in cancer research we stumbled upon an unexpected surprise.

The good news is it’s aimed at an intractable target where there is a high unmet medical need across a range of different cancers and recently entered clinical evaluation.

The bad news is the outcome is uncertain (as yet), plus there are some key challenges we have identified.

Somewhere in between lies the truth of the matter, although there are a few clues where we can put some stakes in the ground as reference points to come back to.

In our latest assessment, we take a look at what is known as well as some of the potential unknown unknowns, and how they might impact the eventual outcome.

We weren’t as excited as many were at ENA22 with an entirely different approach, yet this one piqued our interest and may have more promise…

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