Biotech Strategy Blog

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

Posts tagged ‘IL-15’

Last week we talked about finding ways to make the T cells work harder and smarter – there are numerous ways to do this, but cytokines might be one interesting way to begin the search.

What about NK and other immune cells though, can we do the same with these too?

This week we are focusing on various cell therapy approaches with some academic and industry interviews to share, along with some analysis of arising issues as well as some new developments to review and discuss.

In the first of the series, we have an academic thought leader in the spotlight who had a few interesting points to make on novel cell therapies…

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A high tide marker stands out on the beach, what stood out at ASGCT20 for you?

As Covid–19 continues to exert its impact on the cancer conference schedule, the good news is that it isn’t a total wrecking ball effect as organisations turn to virtual meetings to enable researchers to share their work.

Some of the events we have ‘attended’ this year have been prerecorded in advance, while others have taken the form of live events. Having listened to both, I can say they have advantages and disadvantages either way.

To me, it doesn’t really matter if you are flexible and appreciate the effort the scientists are making to show their wares.

This week it’s the turn of the American Society of Gene and Cell Therapy (ASGCT) to be in the spotlight with a truly ‘live’ meeting.

In the latest post, we focus on some key Gems from the Poster Halls…

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Time to unlock some novel IO targets?

Continuing our latest four part mini-series, this one is on novel targets and agents and we now turn our attention to immuno-oncology in the last two articles pertaining to this particular topic.

You can read the first two articles on targeted therapies here and here.

For the avoidance of any doubt, this latest review is not about T cells, far from it.

Instead we cover six different areas, most of which are related or integrated in some shape of form.

There’s a lot of promising new science now coming out to help us better understand the underlying biology and also think out of the box about ways to enhance or improve on existing research.

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Some of the upcoming coming small biotechs caught our attention and may turn out to be future stars

National Harbor – There were quite a few gems in the poster halls and oral presentations from up and coming small cap biotechs at the Society for Immunotherapy of Cancer (SITC) meeting this year.

Who were they and what did we learn from them?

In the latest part of our latest SITC coverage we highlight 13 presentations – 11 from small biotechs and 2 academic abstracts – that caught our attention, explain what’s intriguing about them and why they matter.

There’s not a single big Pharma included (unless as a reference point or given in combination) since the focus is mainly on up and coming companies with their novel approaches.

The list is quite selective and not at all random from a list of over 850 abstracts.

So what stood out and what was special about them?

Some of the selections are likely hidden sleepers that few will be familiar with… they also cover a wide range of approaches, targets, different modalities and even strategic intent.

Even if you were at the SITC 2019 meeting, increasingly there were more business meetings taking up valuable time than sessions attended, so this is a great way to catch all the highlights for your trip report 😉

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Continuing our cytokine series, we now switch horses from a creative new therapeutic utilising red blood cells that Rubius Therapeutics are pioneering to a very different technology involving synthetic amino acids, in what is known as a ‘Not Alpha’ IL–2 approach from Synthorx.

We have covered new developments in IL–2 based cytokines from Roche and Nektar previously, so what’s cool about the alternative early development that is THOR–707?

To find out, we conducted an expert interview with Synthorx’s Dr Laura Shawver and learned some fascinating details about their novel platform that is sending new molecules into the clinic in the very near future.

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T lymphocyte    Source: Dr Triche, NCI

It’s time for an update on cytokines as there is a lot going on here across both academia and industry.

While the clinical proof of concept has been demonstrated for IL-2 with FDA approval going back to 1992, there’s still much that we don’t know when it comes to the telephone directory containing many of the others.

There’s quite a few questions that can be asked:

  • Which ones might be best in which tumour types?
  • What about timing, dosing, and sequencing?
  • Which early combinations look promising in terms of unleashing the T lymphocytes?

After all, let’s not forget that some cytokines will induce negative immunosuppression, while others might induce variable effects depending on what they encounter in the tumour microenvironment.  It’s certainly a lot more complicated than many people truly realise.

There’s also the much under-rated potential to combine cytokines with other approaches such as immune agonists in order to jumpstart the colder tumours.

In this latest update, we take a look at five very different approaches and see how much progress is being made with alternative forms of immune modulation – the resulting conclusions might well surprise quite a few readers!

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In this post, it’s time to put your thinking caps on and empty your minds of any pre-conceived bias in order to play the modern version of Star Trek tridimensional chess aka IO combination trials.

Gems from the Poster Halls

Here we weave now together some important themes and highlight intriguing ideas that at first seem dissimilar, but actually have much more in common than many realise.

Data from bone chillingly cold poster halls of conferences in the distant past can come back and reviewed afresh in the light of new developments. The seasoned observer discards neither these findings or thought leader snippets of insights within nor forgets them in an instant, as many do after the hum of instant live reactions passes.

With oncolytic viruses and cytokines being much in the news of late, what can we learn about where things are likely headed?

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National Harbor, MD – Day 2 of #SITC17 brought some interesting highlights on a number of fronts, not all of which may be apparent at present, but there are a few readouts that will have a broader impact going forward.

SITC 2017 Stars?

As we move into an era where we see more combinations evolve in immuno-onology, things are likely to get more confusing rather than less so and it could well be another 3-5 years before things truly settle down and more concrete trends emerge.

Here, we reviewed 10 different areas of interest with a strong clinical relevance and explored the topics further.

Please note that some of these will also have follow-on posts with thought leader interviews and related poster reviews.

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The latest company immunotherapy announcement is from Lilly and Nektar Therapeutics, for a strategic collaboration to co-develop NKTR–358, which targets the IL–2 receptor complex, thereby impacting regulatory T cells (Tregs). It is thought that this target may have particular relevance to autoimmune disorders and other chronic inflammatory conditions. This agreement involves an initial payment of $150 million, with the potential for up to $250 million in additional development and regulatory milestones.

Source: Nektar Therapeutics

Preclinical data on this novel compound was recently presented on July 10th at the World Congress of Inflammation.

We first spoke to Nektar at SITC in November, including an interview with one of their leading scientists (Dr Jonathan Zalevsky) together with the academic PI (Dr Adi Diab), and I’m delighted to say that the dynamic duo graciously agreed to a follow-up discussion at ASCO last month on the emerging IO pipeline.

In our current analysis and commentary on the IO pipeline, we also look briefly at the Lilly deal with NKTR–358 in autoimmune disease.

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National Harbor Maryland

National Harbor, MD

The range of different types of cancer immunotherapies in the clinic now is fairly broad, with many promising approaches being evaluated.

Cytokines, despite their initial challenges with toxicities, are an essential pillar of this approach, along with checkpoint inhibitors and agonists, adoptive T cell therapy, and now even neoantigen approaches and cancer vaccines.

Nektar Therapeutics ($NKTR) are developing two intriguing immuno-oncology compounds based on cytokines, which are in early development called NKTR–214 and NKTR-255.

The idea behind this approach is that they are immuno-stimulatory therapies designed to expand T cells and Natural Killer (NK) cells directly in the tumour microenvironment, thereby increasing expression of PD-1 on these immune cells.  Subsequent checkpoint therapy could potentially be made more effective. We already know that those patients with few or no T cells are less likely to respond (cold or non-inflamed tumours) so the hunt is on finding ways to address this particular challenge.  Can it be done therapeutically?

Data was presented this past weekend at the Society for Immunotherapy of Cancer (SITC).

Was the data encouraging enough to justify further clinical development or is this a compound headed to dog drug heaven?

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