Biotech Strategy Blog

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

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Tackling immunosuppression with a dual approach to TIGIT and adenosine

In the second post of the day on overcoming immunosuppression and a hostile tumour microenvironment, we take an extended look at the TIGIT and adenosine pathways through the lens of a company active in both of these niches.

Karl the Fog in San Francisco

What are they doing and, importantly, why are they taking a particular approach?

Where might they also be going in the future?

In our latest expert interview we offer not one, but two, biotech executives from the context of the science and biology driving their commercial strategy.

With the latest announcement yesterday that their key phase 2 trial will continue and data to be presented at an updated medical meeting, there’s a lot to learn and some key pointers to think about.

BSB subscribers can read more on our latest look at a clinical stage biotech company active in the cancer immunosuppression space – you can log-in or click to access our ongoing oncology coverage.

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Tackling a hostile tumour microenvironment on multiple fronts

It’s time to talk about new developments in immunosuppression and some of the different ways in which companies are tackling the hostile tumour microenvironment.

Obviously there are many potential culprits from neutrophils, macrophages, myeloid derived suppressor cells (MDSCs), adenosine, Siglec–15, and TGFβ to mention a few. There are others to consider as well, as we discuss with our latest experts in the hotseat.

Over the next couple of posts we will be highlighting different pipeline agents, along with in-depth expert interviews to explore some intriguing early or emerging approaches. Some are in preclinical getting ready to enter the clinic, while others are already being evaluated in phase 1/2 studies.

In this example of the genre, we had fun catching up on a biotech we first talked to a couple of years ago about their fledgling pipeline. How is doing now and what are they up to?

BSB subscribers can read more on our latest look at a clinical stage biotech company active in the cancer immunosuppression space – you can log-in or click to access our ongoing oncology coverage.

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Making a difference in aggressive lymphomas

Lugano is such a glorious place to hold a cancer meeting!

You can tell how much fondness attendees and presenters have for a meeting location when many start off their talk with a shot of the scenery and remember fond times of past conferences.

Lugano and the International Conference on Malignant Lymphoma (iCML) – held every two years in odd numbered ones – is clearly one such event.

It is here where we learn about the broader context in terms of how various phase 3 trials truly fit in the landscape and whether or not they are practice changing, what the skinny is on a raft of new products in a given category from practitioners in the trials, including problematic or emerging side effects, or how agents might be more effective in one particular subset but not another, and so on.

This year’s meeting is no different despite the virtual nature of the event.  After a couple of recent on-line meetings were a bust due to an inability to host the volume of attendees, one might be forgiven for being a tad nervous this one might go the same way – but these fears were not realised, I’m delighted to say!

Instead, we were treated to a very well organised event with a series of high quality talks and posters on a variety of lymphoma related issues, including rapid turnaround for the on-demand recordings the next day for any sessions one missed.

BSB subscribers can read more on our latest look at key hematologic developments relating to lymphomas  – you can log-in or click to access our ongoing oncology coverage.

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New developments in hematologic malignancies to make your head turn

Years ago it used to be that whenever we mentioned hematology trials or new products in development outside of the ASH meeting there was a distinct drop off in attention… with the blossoming of many new therapetic approaches, oh my, how things have changed!

Lymphoma cells  Source: NCI / Dr Lance Liotta’s lab

As we segue between the EHA and iCML conferences I wanted to highlight a couple of important developments, which may well have disappeared off many people’s radar.

As we gather additional clinical evidence with more patients and longer follow-up at therapeutic doses over time, I find myself struck by how much these oft forgotten agents might actually have some legs, meaning they look promising enough to be considered as potential approval candidates.

Obviously a randomised controlled phase 3 trial will likely be needed at some point, but given the attractiveness of the data so far, more observers would do well to pay attention to these compounds, especially as they are not from companies we traditionally think about about in terms of hematological malignancies.

These two selections have grown quite a bit since the first-in-human trials with noticeably much more robust data to evaluate and consider…

BSB subscribers can read more on our latest look at early key hematologic developments – you can log-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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A look at 6 key developments in advanced hematologic malignancies

Stacking up the evidence

Not everything at ASCO is necessarily focused on solid tumours, there’s often some useful hints of progress on the hematologic malignancies front too.

Here we look at the building evidence for half a dozen such developments across myeloma, lymphomas, and acute leukemias.

To be clear this doesn’t mean they will all be of the good news type because sometimes early developments promise much and fizzle out over time.

This is the advantage of following compounds and technologies in new product development over time – you get to see them as they really are and not through the lens of rose tinted glasses….

BSB subscribers can read more on our latest update regarding immunotherapies not checkpoint blockade in hematologic malignancies  – you can log-in or click to access our ongoing ASCO21 coverage.

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Shipping the KRAS line

For students of anti-cancer drug development and history there’s a really nice review paper just published on some of the lessons learned from targeting the RTK/RAS/MAPK pathway, including KRAS, from the lens of structural biology.

There are plenty of examples shared using crystallography, as well as some important highlights along the way. They also mention the SHP2 molecular glues, which launched a new era in this niche with a flurry of companies and novel compounds rushing to evaluate their sparkly new SHP2 inhibitors in various dose escalation and expansion trials.

We’ve been following this niche since NIBR scientists reported important preclinical results with their probe molecule (SHP099) an allosteric inhibitor, which changed how many looked at phosphatases – finally it was a druggable target!

Fast forward five years and this weekend we heard the results from the improved clinical stage compound, TNO155, in an initial clinical readout from Novartis coming on top of the early data from Revolution Medicines at AACR with their SHP2 inhibitor, RMC–4630.

What did we learn and where are the company going with their approach?

Following presentation on the dose escalation cohort at ASCO over the weekend we received a bunch of reader questions and had some of our own too, so some expert commentary is included from the sponsor of the trial, Novartis.

BSB subscribers can read more on our latest update regarding SHP2 and RAS addicted cancers – you can log-in or click to access our ongoing ASCO21 coverage.

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Which early phase agents look promising – or not – ASCO21?

New product development and early phase anti-cancer agents have been very much a focus on BSB (and PSB before it) since their inception.

It’s fascinating to realise one of the compounds selected for review in this article has its origins in a much one earlier trial with serious incidents we saw in a trial in novel volunteers with a different company and product and originally inspired the beginning of our scientific writing in 2006.

By an interesting quirk of history, the first time we wrote about PARP inhibition was in the same year and now it is one of the selections in the ASCO plenary today.  You can read more about the olaparib OlympiaD trial write-up here, proof that all successful products eventually started off in developmental therapeutics at some point in their early career!

In this latest review, we selected eight anti-cancer compounds currently undergoing phase 1/2 trials and put them through their paces… some are more positive than expected, some were downright disappointing, some were off to an encouraging start, others the count is out until we see more robust data.

How is the report card looking this year?  Some reflections and thoughts to consider…

To find out, BSB subscribers can read more on our perspectives regarding Developmental Therapeutics and various early stage compounds, subscribers can log-in or you can click to read our ongoing ASCO21 coverage.

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Unheralded developments in renal cell carcinoma

Graffiti in Adams Morgan, Chicago

Not in Chicago – It’s fascinating in a way that while there’s often much time and attention devoted to the big three cancers of breast, lung, and prostate carcinomas, genitourinary cancers such as renal and bladder are often forgotten or sadly ignored.

Not here on BSB – we probably write as often on this segment, as we do about the other categories.

The good news is there are some key abstracts we are looking forward to hearing more about this year with either important top line results to ponder or some detailed biomarker analyses coming out.

As we wait for the digital poster hall to open, it’s time to switch focus from the hurly burly of yesterday’s news…

BSB subscribers can read more on our perspectives regarding renal cell carcinoma, subscribers can log-in or you can click to read our ASCO21 coverage.

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Is olaparib scaling new heights in OlympiA?

Source: Wikipedia

We first wrote about the fascinating and complex space way of synthetic lethality and PARP inhibition way back in 2006 when the early preclinical developments and targets were just emerging and finally here we are – 15 years later – with the very first phase 3 data in the adjuvant setting.

It’s not often I get to highlight someone and their extensive research from my alma mater, but it’s a delightful opportunity to put it on the front page for a change. The gritty urban setting is a far cry from the romance of the other Kings College (in Cambridge), although the two cities do overlap somewhat in this particular story.

What can we learn from the latest clinical development in early stage breast cancer and what don’t we yet know?

There’s actually quite a lot to ponder and digest here…

BSB subscribers can read more on our initial perspectives regarding PARP inhibition in early stage breast cancer and the OlympiA trial, subscribers can log-in or you can click to read our ASCO21 coverage.

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