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

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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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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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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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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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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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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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Pierre de Coubertin Statue, Atlanta

On BSB we write about the science driving innovation in the biotechnology and pharmaceutical industry, and how that translates into new product development.

One of our favorite meetings of the cancer conference calendar is the annual meeting of the American Association for Cancer Research (AACR). The 2019 annual meeting starts in Atlanta later this week and is the cancer research mecca that we and others will be heading to later this week.

Ahead of the meeting we’re continuing our #AACR19 previews with a look at some of the innovative, novel cancer agents we expect to hear more about in Atlanta.

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Imagine being becalmed on boat in the doldrums patiently waiting for the wind to pick up…

Just as experienced sailers learn to make best use of the available knowledge on sea breezes, tides, tidal winds, catspaws, headsails, heels, genoa etc, so immunologists are experimenting with various modalities.

This enables them to develop a more extensive knowledge base before they can use all the available tools more effectively at their disposal in order to chart a course in each tumour type and setting.

That’s a tremendous amount of information and skills that needs to be gathered before we can even consider racing against competition. So it is with cancer immunotherapy, with all its different approaches that are available to combine or sequence in a multitude of tumour types. We are still largely in the unknown unknown stage of figuring things out.

That said, each cancer conference brings new nuggets and gems that on their own do not appear to offer much, but added together in the broader picture can contribute more than many observers realise.

That was certainly the case with our latest update on IO therapies, as you will see…

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The annual ASCO-SITC meeting (#ImmunoOnc19) was held in San Francisco this year and has come a long way from the inaugural event we attended in Orlando.

Finding the signals amongst the noise

In the original 2017 event, I vividly recall as stirring presentation from Dr Limo Chen on targeting CD38 in solid tumours, last year we wrote an update on GU cancers including the STING pathway.

What’s in store from San Francisco and how do we go about finding key signals from the noise?

Over the next two posts I’m going to focus on new findings in various approaches that either look interesting and worth watching, or where there are lessons that can be learned for future developments.

This time around, some of the highlights surprised even me…

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Chinese Pagoda in Hoxton

Yesterday on BSB we looked at the emerging landscape in western countries for cancer immunotherapies that target gamma delta T cells. Today we’re turning our attention to China.

There’s a lot of interest in cell therapies in China. Anyone who has seen one of Dr Carl June’s recent presentations will no doubt recall the slide he shows of how many CAR T trials are underway there.

What’s happening with gamma delta T cells in China, and in particular CAR γδ T cell therapies? Do the Chinese have a competitive advantage in this emerging field and what can we learn from some of the results that have been reported?

This is the fourth post in our mini-series on the potential of gamma delta T cells for cancer immunotherapy.

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