Biotech Strategy Blog

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

Posts tagged ‘neoantigens’

AACR19 Preview of Cancer Immunotherapy Sessions – Part 1

We’re starting our review of the program for the forthcoming 2019 annual meeting of the American Association for Cancer Research (Twitter hashtag to follow: #AACR19) with a look at the cancer immunotherapy program.

One of the challenges of a large meeting is that it’s like a smorgasbord or buffet in a hotel that’s resplendent in choices, but you can’t possibly eat it all.

Choices!

Some choose to follow a research area, others a target or tumor type. There’s a lot of ways to segment the program depending on your specific interests.

However, it’s a good idea to have a plan in place ahead of a large conference such as AACR, even if you modify it as you go to take into account evolving needs.

Seasoned conference goers will be familiar with the maxim known as “the law of two feet” – if a session you are in doesn’t live up to expectations or meet your needs and something else looks more to your taste from the tweets, then simply dash off to another!

In our latest conference preview, we’ve taken a careful look at the cancer immunotherapy track.

What are some of the key sessions to put on your calendar if you’re following this track or have an interest in this area?

In Part 1, we review the IO sessions from Friday to Sunday then tomorrow in Part 2, we’ll review the schedule from Monday to Wednesday.  Yes, it’s that intense this year! Just think, five years ago you had to search the program really quite hard indeed to even find much on immuno-oncology, as it was very much in its infancy then.

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Where are the next Immuno-Oncology breakthroughs coming from?

Barcelona: What makes a great scientist is not accepting conventional wisdom or dogma but instead thinking differently, pursuing what data generated truly means, and asking if we can do things differently as a result?

Gaudi architecture, Barcelona

Current success in immuno-oncology new product development has been built on basic research done twenty and thirty years ago, when many didn’t believe in leveraging the power of the immune system therapeutically.

At the ongoing European Association for Cancer Research (EACR) “Defense is the Best Attack” meeting in Barcelona this week, many experts in the IO field are sharing novel findings on what may lead to future insights.

What were some of the key take-homes?

Subscribers can read our notes from some of the presentations that stood out at the meeting.

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Can we target p53 therapeutically?

The Francis Crick Institute in London has an admirable program of engagement with the public and external researchers.

Attending a Crick Lecture recently presented by Cancer Research UK (CRUK) Chief Scientific Officer, Prof Karen Vousden CBE FRS, reminded me of my days as a PhD student at nearby King’s College London.

Regular BSB readers will recall that Prof Charles Swanton FRS is the Chief Clinician of CRUK.

In her Crick lecture, Prof Vousden elegantly explained to the audience why p53 mattered and how it might be targeted by small molecules.

What is the potential of this research for translational drug development? In this post, we take a look at new developments in the basic understanding of what p53 does, the current state of targeting p53 and Prof Vousden’s latest approaches.

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New developments in cytokines as immune modulators

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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Iraj Ali leads the way at Achilles Therapeutics

There is a lot of interest of late in targeting neoantigens in cancer therapeutically.

At the recent European Society for Medical Oncology (ESMO) meeting, we heard Dr Patrick Ott from the Dana-Farber Cancer Institute present the latest clinical data for Neon’s cancer vaccine approach (See: interview with Dr Ott).

If you have an interest in neoantigen based cancer treatments, however, then a company on the horizon that we’re excited about is Achilles Therapeutics.

It’s an early stage private UK company, in what is very much still a developing and emerging field. Founded just over two years ago, it has a strong academic pedigree. The scientific co-founders are Professors Karl Peggs, Mark Lowdell, Charles Swanton and Sergio Quezada.

BSB readers will recall our prior interviews with Prof Charlie Swanton FRS (See: here and here), where he talked about the groundbreaking TRACERx study he’s leading, some of the insights it is generating regarding neoantigens, and their importance in cancer evolution.

Achilles Therapeutics was established to commercialise the intellectual property being generated from the TRACERx program.

While in London en-route to ESMO18, the CEO of Achilles Therapeutics, Dr Iraj Ali kindly spoke to BSB about where the company is, and some of its future plans.

From what we heard, it’s definitely a company we can expect to hear a lot more about in the cancer immunotherapy space. Check it out!

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What did we learn from Neon at ESMO18?

There’s a lot of excitement in the field of personalised neoantigen based vaccines and cellular therapies. One of the companies leading the way in this niche is Cambridge, MA based Neon Therapeutics.

Neon Therapeutics – Open for business

At the recent European Society of Medical Oncology Congress (ESMO18) in Munich, one of the much anticipated presentations was the preliminary clinical data for Neon’s personalised neoantigen cancer vaccine (NEO-PV-1).

This was the first data for Neon’s product, as opposed to the work done by Prof Cathy Wu and colleagues that used an academic version of the cancer vaccine (NeoVax).

We heard the initial results for the NT-001 trial that began in November 2016 to explore the combination of nivolumab plus NEO-PV-1 in people with certain metastatic cancers.

In this post, we take a closer look at what the trial told us, why the data failed to impress some, and asked was their commentary fair or should we look at the results differently?

The data was presented by Dr Patrick Ott, who is an Associate Professor of Medicine at Harvard Medical School and Clinical Director of the Melanoma Center and the Center for Immuno-Oncology at the Dana-Farber Cancer Institute in Boston. He kindly spoke to BSB and offered his candid perspectives on the data presented in Munich.

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Preview of CICON18 – Part 2

Increasingly we are seeing more research on the inflammatory status of the tumour microenvironment (TME) in recent years, not to mention the impact of cytokine and chemokine signalling pathways, and how they can be manipulated therapeutically.

There’s also a much wider range of novel immunotherapy approaches being evaluated such as checkpoints, CARs and vaccines with respect to both T and NK cell therapies. There are also a few other immune cells being targeted for developmental therapeutics.

As part of the ongoing CICON18 Preview series, we take a look at what’s in store and why the latest ten we’ve highlighted matter in the broader context of the evolving landscape…

For those who missed it, Part 1 can be found here.

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Why don’t all cancer patients with a high TIL respond to immunotherapy?

One thing that often comes up is why don’t all inflamed tumours respond to immune checkpoint blockade or immunotherapy – it is that PD-L1 is a weak biomarker of response or are there factors that can explain the phenomenon?

ASCO 2011 #BlisterWalk

The ASCO #blisterwalk

Some new research now sheds some light on the issue.

This seemed to be a great opportunity to explore several topics around this theme and look at what the data from AACR and ASCO are potentially telling us.

Obviously we need to see the presentations in Chicago to be sure, but the good thing is that there are some good hints of where to start and what to think about going forward since they could have an impact on clinical trial design.

With a lot of observers focused on some disappointing results from, for example, Incyte’s epacadostat (IDO) and Jounce’s ICOS antibody, are there things we can do to improve the chances of success?

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Key Highlights From AACR Molecular Targets Day 1

Philadelphia: Biotech Strategy Blog is in Philadelphia for the AACR-NCI-EORTC Molecular Targets  and Cancer Therapeutics Conference (aka known as ‘The Triple’) that starts today and goes on over the weekend until Monday.

Molecular Targets has always been one of my favourite meetings!

Coming here is a reminder that despite the excitement and promise of immunotherapy, there is a lot still happening in cancer research on targeted therapies, as well as the intersection of the two. I expect many of the thought leaders here to be talking about the challenge of how do we combine targeted therapy with immmunotherapy to best effect.

I don’t think there will be much on social media since much of the work discussed here is unpublished and we don’t tweet that, but if you do want to follow along, the Twitter hashtag is the memorable #Targets17. There’s also an app you can download to see the full program etc.

For BSB subscribers, over the weekend we’ll be providing a daily summary post at the end of each day on key topics, issues, and themes we’ve picked up during the meeting.

Today, there was a press conference at 9.15am with the three meeting co-chairs:

What did Drs Ribas, Gulley and Swanton have to say about what we can expect from the meeting and some of the key themes and noteworthy abstracts presented?

Stay tuned for more!

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Immunotherapy Possibilities in Pancreatic Cancer

Pancreatic adenocarcinoma is a tough disease to deal with given that it is portends poor clinical outcomes, aggressive tumour biology, and early metastatic spread. Not surprisingly, we have seen very little improvements in terms of clinical outcomes with anti-cancer therapeutics. Surgery (for early stage disease) and intense chemotherapy (for metastatic disease) remain the bedrocks of treatment to this day.

From an immunotherapy perspective, there are also additional barriers and hurdles to overcome including, for example, lack of high mutational load, a complex inhibitory tumour microenvironment, and even a physical barrier in the form of the stromal layer.

Not surprisingly, all of these factors combine to make companies reluctant to rush into clinical trials with immune checkpoint blockade, accepting that we really need to understand the underlying tumour biology better before attempting such an endeavour.

At a recent cancer conference we heard an uplifting talk from a research group who are attempting to tackle this issue and offer some pointers on where there may be some near-term opportunities that are worthy of discussion.

Before we can even consider what delivery system or adjuvant to use, we first have to do the scientific investigations into what’s special about exceptional responders and characterize those.

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