Biotech Strategy Blog

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

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Dancing with proteins

I must confess that a preclinical session I wandered into back in 2008/9 after getting lost in the far corner of a conference centre included brief details on an experimental 4–1BB CAR-T cell construct was both unusual and intriguing at a time when monoclonals and TKIs were all the rage. Who would have guessed then, though, that the fledgling idea would go onto leading a revolution in a new type of therapeutic approach that is becoming more commonplace a decade later?

Learning from preclinical developments is therefore a great way to understand what we might see in the future, however weird and wacky it may appear at the time. While many new concepts may not see the cold light of day, they can contribute in some small way to incremental improvements. After all, scientists are always looking to refine, enhance, and improve on what we have through knowledge, so we shouldn’t really be surprised when intriguing new ideas eventually start filtering through. There’s always a better way to do drug a target or find a new target.

Untangling proteins

With this mood in mind, we have already highlighted several areas where knowledge and creative scientific thinking is starting to evolve into new compounds, with other ideas yet to be fleshed out.

Today, we offer a new thought leader interview in this genre, where a relatively young biotech are doing something completely different and thinking creatively outside the box.

Whether their novel ideas will lead to a future blockbuster is anyone’s guess – we can certainly applaud their thinking and endeavour in trying to push the boundaries of what’s possible in an endeavour to change things for the better…

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There is a deeper world than this

Padstow, Cornwall – It’s May Day or ‘Obby ‘Oss, as it’s known locally in this little corner of south west England.  The quaint festival means that it’s the biggest day of the year as over 30,000 people crowd into the tiny fishing village.

Obby Oss Blue

Centuries old traditions are still alive and well in this part of the country and the big question of the day (are you red and white or blue and white?) is a far cry from the complex high tech world of cancer research.

Still, with all the time and attention focused on immunotherapy and targeted therapies of late, it is all too easy to forget what’s happening on the epigenetics front, which is quite a bit in practice.

We often see random allcomer approaches to clinical trials, which are find for phase 1 studies where you want to gather data on responders and non-responders in order to conduct PK/PD and immune profiling, as well as biomarker and signature development, but a potential recipe for disaster in phase 3 if you have no idea exactly what’s driving the efficacy since you can all too easily end up with unbalanced arms that you didn’t control for and thus skew your survival curves in a way you didn’t anticipate.

Why on earth would you use a targeted therapy in an untargeted fashion? Hmmm obvious question and yet, many companies still do this all the time.

There are some biotechs out there, I’m pleased to say, who do conduct extensive translational and biomarker research.  Obviously finding those markers is a lot more tricky than choosing red or blue.

One biotech company we have been keenly following for a while is Syros.

We first wrote about them in Spring 2014 and now, five years on, I thought it would be a nice idea to catch up with one of their founders and learn more about the science underpinning what they’ve done and where they’re going with future projects. Not only do they invest in smart medicinal chemists, profiling and translational research, but they also seek to identify rational reasons why people respond to their compounds.

The answers were rather interesting and there’s quite a bit that readers might be curious to learn more about…

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Going back to basics

We have written about a huge variety of different approaches to cancer research since 2006 but few are as intriguing as using pathogen-based approaches involving viruses or bacteria to stimulate or re-activate the immune system. After all, when such foreign bodies break through the physical barriers and enter the bloodstream, the immune system instantly springs into action to tackle them.

Can this knowledge be used effectively in the design of anti-cancer therapeutics?

We have seen some promising initial results with oncolytic viruses, but what about bacterial based approaches?  Can a different approach to drug scaffolds yield improved results?

Here, we look through the window at a novel platform using immunotoxins in early development that may well pique a few people’s interest and offer our latest thought leader interview discussing the approach…

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Chipping away at cancer

As we follow the journey of various neoantigen and neoepitope approaches from start-up and preclinical research through to the clinic, it’s been interesting to see how different companies and academic research groups have chosen to consider their R&D strategies.

Some of the companies we’ve interviewed and highlighted in this space include Neon Therapeutics, BioNTech, Gritstone, and newcomer, Achilles Therapeutics, along with various academic programs such as George Coukos’s neoepitope vaccine approach in Lausanne.

After we first spoke with Gritstone a couple of years ago, things seemed to go a bit quiet on the western front while Neon, BioNTech, and Achilles all had news to talk about. It’s always hard to choose from rock-paper-scissors and this may well be another modern twist of that genre until clinical data proves otherwise.

That all changed with more data being presented by the California-based biotech recently, plus patients are also being enrolled into their first neoantigen clinical trial.

At a recent conference, we caught up with their CMO, Dr Raphael Rousseau, to find out more about where they are and importantly, where they’re headed…

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Targeting the adenosine pathway in cancer immunotherapy

The AACR19 ‘mosh pit’ where gems abound

It’s been a while since we looked at the adenosine pathway, where a fog of immunosuppression is thought to cloak the ability of the immune system to induce antitumour immunity.

When we first wrote about the A2A receptor-CD73-CD39 pathway in 2016 there really weren’t very many players in this niche.  Since then the field has expanded quite considerably and there are now more companies and molecules to consider.

As we straddle AACR and ASCO, it’s a great time to offer an update and look at what we learned…

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Are 𝞬𝝳 T cells immuno-suppressive and should we delete them?

We’re continuing our series following the development of novel cutting edge strategies targeting gamma delta (𝞬𝝳) T cells, with a look at the two approaches Puretech Health are pursuing based on the research of Dr George Miller (NYU Langone).

Data was presented at #AACR19 for a first-in-class immunotherapy targeting immune-suppressive delta 1 containing 𝞬𝝳 T cells and one targeting Galectin–9.

Drs Panchenko and Filipovic at their AACR19 poster

We recently spoke with Dr Aleksandra Filipovic, therapeutic lead for oncology at Puretech Health, she’s pictured right with Dr Tatyana Panchenko from NYU Langone at their AACR poster.

Dr Filiopovic told BSB that Puretech are looking for the next big IO breakthrough:

“We looked at this landscape and the massive amount of trials going on. We said ok, if we’re going to go into the space of immuno-oncology, what is it that we need to do differently in order to, upfront, try and ensure that we’re going after targets which could be the next PD–1. Our thinking went along the lines that we would really need to identify those next checkpoints, those next foundational modulators of the immune system.”

This is the first of two interviews from #AACR19 on novel strategies to target 𝞬𝝳 T cells, an emerging area that companies are looking at with both antibody and adoptive cellular therapy approaches. Do check out our previous mini-series if you missed it.

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Going beyond PARP inhibitors to improve cancer outcomes

DNA Damage Repair (DDR) has come a long way over the last decade or so from preclinical development through clinical trials, including some notable failures along the way. What began initially with PARP inhibitors, has now expanded into other related targets in the pathway, including ATM/ATR, WEE–1, Chk1/2, DNA-PK, and even Fanconi anemia genes such as FANCA/BC/D1, BRIP1 and PALB2, which are considered an indication of BRCAness where there is also chromosomal instability and homologous recombination.

Top 10 DDR targets and molecules at AACR19

At AACR last week, there was plenty to learn about in the ever-expanding DDR niche in terms of new data from a relatively new target such as DNA-PK to updated clinical data on WEE–1 and Chk1 inhibition to early data on PARP in a new tumour type to add to the growing list of ovarian, breast, and prostate cancers that are impacted by DDR therapies.

Included in this post are 10 key targets or molecules in the DDR niche that are of potential interest to readers – we explain why we included them and why the data matters.

Here we take a look at the highlights that we came across in this mini review, which should be useful preparation ahead of yet more clinical data likely being presented at ASCO and ESMO later this year.

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The Wisdom of Crowds

Atlanta – what’s exactly behind a poster board mobbing at AACR?

AACR19 Poster Hall

Is there some science or rationale behing the attention or is it something quite quirky and unexpected?

That was the critical question we wondered about as we traversed the poster hall sessions over the last few days and noticed the certain posters received more attention than others:

  • Why was this?
  • Is there a rhyme and reason to it?
  • Which ones were actually mobbed?
  • Is the attention justified?

If you’re curious like we were, then this is the post for you.

We highlight several posters from the AACR19 conference that received a noticeable amount of traffic and in future posts we will highlight those we consider to be gems from the poster halls and explain why, which… wasn’t necessarily quite the same thing (as being mobbed).

So without much ado, which ones were in the spotlight by AACR attendees this year?

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Is the Apexigen anti-CD40 data hit or miss?

Packed sessions at AACR19

Atlanta – We’ve had a few requests to discuss the Apexigen anti-CD40 data presented by Dr Robert Vonderheide (Penn) presented at AACR19 on Sunday.

That’s a request we happy to oblige.

There seems to be quite a difference in reactions between researchers and investors on this issue, so it’s a nice opportunity to put the data in appropriate context.

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Five early emerging trends to note from AACR19

Atlanta: There is no shortage of innovative and potentially ground-breaking science on display at the annual meeting of the American Association for Cancer Research (AACR) that’s currently taking place in Atlanta.

AACR19 Poster Hall melee yesterday afternoon

What is noticeable this year is the large number of scheduling conflicts, i.e. interesting sessions or symposia all going on in parallel and that’s not including the poster sessions, where much of the early work is presented – you could spend much of the meeting in the poster hall alone!

It’s impossible for any outlet to do the meeting justice, so our selection of topics is subjective in nature.

We’ll be posting interviews and more in-depth pieces later, but in this post we take a look at what stood out for us in the Friday/Saturday education sessions we attended and in Sunday oral symposia.

As Frank Sinatra famously sang, “The best is yet to come,” with a tsunami of presentations and posters slated to be heard over the next few days.

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