Blog | Biotech Strategy Blog

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This year’s crop of emerging agents and targets are a very different bunch altogether and the breathless hype has been replaced by much more quiet determination and optimism.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

To continue reading our latest highlights on oncology new product development including commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

The Fall and Rise of Essa Pharma

Today’s post highlights the lessons learned as part of the trial and tribulations associated with oncology R&D, including a large dash from vibe of the famous British sitcom, “The Fall and Rise of Reginald Perrin.”

Madrid city centre at dusk

No matter what industry outsiders think, drug development very rarely goes in a straight line from A-Z since there are often many expected – and even unexpected – twists along the way.

The company we’re focusing on is Essa Pharma, and boy, do they have some challenges and unexpected plot twists as part of their corporate DNA!

I often hear from artistic friends paraphrasing Ursula Le Guin that it’s all about the journey, not the destination.

Except in business and especially in Pharmaland, however, it is entirely about the destination and how you get there doesn’t matter so much. After all, if a small biotech doesn’t get a product in development over the finish line (aka approval) and become a commercial success then it’s game over for everyone involved.

This is one of those kind of stories.

A tale of belief, tension, tenacity, re-tooling, and finally, renewed hope…

To continue reading our latest highlights on oncology new product development including commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

Process is power

If you had to name one company who have executed well in the IO space, it’s hard to argue against Merck with their consistent and relentless efforts from the pembrolizumab clinical development program building a blockbuster niche by niche.

Dawn of a new IO era at ESMO23?

Beyond checkpoint blockade, what’s next?

Are they a sparkly one-horse wonder or are there real possibilities to build a kingdom based on rational combinations?

Not every phase 1 pipeline agent is going to make it to the next stage, never mind over the finish line to market – some folks might think of this as the funnel of shame. The indiscriminate mud flinging which follows an ‘as many shots on goal as possible’ winner takes-all-approach is limiting, however, when you realise it creates an achilles heel in strategic thinking.

Instead suppose you can build a linchpin to enable you to build on while offering a helping hand up to some of your other early products in combination? To do this you need optimised agents which play well when combined. Now you have a very different proposition while raising the bar to other competitors – who may not have similar agents with optimal properties.

In our latest company interview, we explore the progress with several of Merck’s early stage products, look from the lens of how they see them, and where they’re headed…

To continue reading our latest highlights on oncology new product development including commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

Who’s waving the flag at ESMO 2023?

Plaza de Cibeles, Madrid

Our coverage of the annual meeting of the European Society of Medical Oncology (ESMO) continues with a discussion on how we might go about overcoming the development of resistance or immune escape.

In order to accomplish this herculean task we perhaps need to get better at selecting the optimal combination partners in different tumour types, rather than simply taking whatever pipeline agents are available in-house and throwing them together.

The good news is there were some elegant and unexpected successes reported over the last two days, although they were offset by a few trial oddities producing negative results.

In our latest coverage, we look at examples in each category to explore what lessons can be learned from the body of evidence presented so far…

To continue reading our latest highlights on oncology new product development including commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

How bispecific antibodies are reshaping cancer treatment

Rolling into Madrid!

One of the challenges we are starting to see more attention on is what happens in later lines of treatment for advanced solid tumours, regardless of whether prior therapy involved chemotherapy, immunotherapy, or hormonal therapies.

How can we provide new options for treatment of refractory disease and help more people live longer?

Finding active drugs with both a reasonable safety profile and demonstrable solid activity in a situation with more complexity in terms of the underlying biology coupled with a much higher tumour burden has long been a challenge for many oncologists and companies.

In previous years we saw how poorly checkpoint inhibitors did in this setting compared to using them upfront and while chemotherapy is very effective at shrinking tumours, the effects are rarely long lasting.

What’s next then?

One approach involves bispecific antibodies where the tumour cells and T cells are literally dragged into closer proximity, enabling the serial killers to do their job more effectively. They worked rather nicely in blood cancers, so why not in solid tumours?

After nearly a decade of trying out many permutations of this approach, we are finally starting to see some light at the end of the tunnel with several different agents in diverse tumour types…

To continue reading our latest highlights on oncology new product development including commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

The guardian of the genome

Back Bay Boston

With the TARGETS meeting ending and ESMO soon to be starting up, I wanted to offer up a change of pace completely by highlighting some important new cell therapy research presented at the AACR Tumour Immunology and Immunotherapy meeting in Boston.

The CAR-T cell therapy space has certainly seen a lot of developments this year since we wrote about what was coming down the pike in February and here we are in the fourth quarter and the researchers in this niche continue to execute.

I suspect a lot of folks dismissed the first round of gene editing attempts for various reasons without really thinking deeply about why this might be the case and how the issues can be overcome.

This is not the case for the folks at the top of their game – they don’t give up, they go away and find out why things don’t work as expected, how we can overcome them, and importantly, improve on clinical trial execution…

To continue reading our latest highlights on oncology new product development including commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

Scaling the ESMO23 ramparts

Scaling the ramparts in Real Madrido

In our last ESMO23 Preview ahead of the live meeting starting on Friday, we highlight another eight targets to watch out for where there will be intriguing data dropping out from Madrid over the weekend.

More than just the data though, is consideration for the implications of the findings and how they can impact a particular tumour landscape.

One thing to note is just because a company highlights what they consider to be positive data doesn’t always mean it is actually so when you look carefully at the small print.

Not surprisingly there are a few examples of this genre at the forthcoming conference…

To continue reading our latest highlights on oncology new product development including commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

Precision Targeting of Elusive Cancer Oncogenes

Sunset over Boston Commons

Cancer remains one of the most intractable diseases, with certain types and subtypes continuing to evade effective treatment. While great progress has been made with immunotherapies and molecularly targeted drugs, cancers driven by notorious oncogenes like KRAS, MYC, and p53 remain challenging to drug.

These key transcriptional and signalling proteins play vital roles in normal cell physiology, meaning inhibiting them often causes toxicity. However, the allure of tackling cancers addicted to these oncoproteins keeps researchers striving for more precise, selective ways to target them.

One emerging approach is to inhibit a key transcriptional kinase involved in regulating MYC and other cancer-promoting genes. Several inhibitors of this kinase have been tested clinically, but most were either insufficiently selective or too toxic.

A new compound profiled in the post below shows early signs of being a more optimised inhibitor. It displays high selectivity and a long half-life, enabling sustained target inhibition without excessive toxicity. Early data from a phase 1 trial in solid tumours has demonstrated clinical activity, including exceptional responses in MYC-driven sarcomas.

These promising results highlight the potential of this new wave of inhibitors to tackle MYC-dependent cancers, including aggressive lymphomas. Other companies are advancing selective inhibitors of this kinase into clinical trials for hematologic malignancies.

Overall, these precision inhibitors represent an exciting targeted strategy against transcriptional addictions in cancer. The initial clinical success offers hope for making meaningful advances against once intractable oncogenes…

To continue reading our latest highlights on oncology new product development including commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

How to Knock Out Cancer’s Backup Plan

Boston Commons in the Fall

Cancer’s got moves… sneaky moves to ensure its survival when you throw targeted therapies its way.

Monotherapy whacks just one piece of the beast. Crafty tumour cells can simply switch on alternate pathways to drive growth again. It’s like a hydraulic game of Whac-A-Mole.

But what if you could outsmart cancer’s backup systems? Shut down its escape route for a while longer?

New preclinical data reveal a smart 1-2 punch that can trap tumours in a corner. The sweet science of vertical and cross pathway inhibition.

This new technique tags both early and late players in pathways like MAPK and PI3K/mTOR. When this happens, cancer’s got no fallback. Nowhere to run, nowhere to hide.

Tumours take a sustained beating with every line of therapy thrown at them. Signalling disrupted. Proliferation caged. Apoptosis triggered. TKO.

Combinations tested in NSCLC, RCC, CRC and pancreatic cancer. Impressive, durable regressions. Researchers now poised to take this clever combo into the human ring.

Want the insider details? A ringside seat to the science? Step this way and we’ll walk you through the preclinical data blow-by-blow…

To continue reading our latest highlights on oncology new product development including commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

The Next Frontier

Boston in the Fall

One of the joys of small specialist meetings is you can find early data from emerging biotechs or largely hidden abstracts from established companies seeking to avoid too much attention.

In great years, the AACR-NCI-EORTC molecular targets meeting doesn’t disappoint, offering unique insights on gems from the poster halls.

This meeting is also where we first cut our teeth reporting on promising targeted therapies before they became mainstream in 2009 and as such, I still have a soft spot for TARGETS or TRIPLE (when in the US) or EORTC (when in Europe).

The two things I was excited enough to write about that year were Dr Anirban Maitra’s fascinating nanobots as a stealth trojan horse strategy in pancreatic cancer (he was then an assistant professor at MGH) and Dr Mark O’Connor (KuDos) thoughtfully explaining synthetic lethality and PARP inhibition in the drafty poster halls using a three-legged stool analogy… you never forget either concept once you grasp them.

Who knew a little known small molecule then subsequently would go on to become a blockbuster for AstraZeneca as olaparib (Lynparza) and appear in multiple plenary sessions?!

This is ultimately why we love this meeting – who’s the next KuDos-in-waiting and what are the cool next generation developments, which could potentially be disruptive in their field?

In today’s post, we highlight another small, young biotech very much like KuDos were in 2009, only here we are looking at a very different approach to tackling KRAS, NRAS, and BRAF.

How far they will eventually go remains to be determined, but part of the excitement lies in finding engaging scientists who seek to do things differently from everyone else and win in the long run…

To continue reading our latest highlights on oncology new product development including commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers