Biotech Strategy Blog

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

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Posts by MaverickNY

How F-star are optimising bispecific antibodies for cancer treatment

Mononclonal and bispecific antibodies in the immuno-oncology space have certainly had a bit of a roller coaster ride over the last couple of years with various safety concerns including cytokine release syndrome (CRS) and even fatalities coming to the fore following clinical holds on various compounds across several quite different compounds.

Barbara Hepworth sculpture at Downing College, Cambridge

As companies work their way through those issues with FDA and other Health Authorities, can we also learn from our previous experiences with checkpoint blockade, immune agonists and other IO targets in order to develop safer products?

One thing has become clear and that’s how important particular aspects of the engineered molecules can make an impact in terms of both safety and efficacy. There are, after all, quite a few factors that can be manipulated or changed to impact performance, much as the design arrangement and composition of various components into a unified whole is crucial to Formula Once racing cars.

In our second part of the bispecific mini-series, we head over to Europe and interview the CSO of a leading company in the IO bispecific space to learn more about these design features and the potential benefits they might induce.

It makes for rather interesting reading when we consider the next wave of IO clinical trials…

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The Next Wave of IO with Dr Dan Chen

It’s time to launch a new mini-series where we explore some of the issues and concepts surronding a given topic and then look at how they are being tackled through the lens of different biotech companies.

Storm clouds gathering over immune agonists and bispecific antibodies?

The latest topic is bispecific antibodies, a development we have often covered since 2014/2015 here on BSB. Much has happened in that time and many compounds have fallen by the wayside. In my view, this is a normal part of oncology R&D attrition – it’s not that we encounter problems, it’s how companies handle the road blocks along the way that matters.

What can we learn from the first two waves of immuno-oncology that can be applied to bispecific developments?  There is no doubt that while some have been successful in making it to market, quite a few have encountered various challenges along the journey.  Why is that and how to we address the emerging or thorny issues?

Change is inevitable in the cancer immunotherapy revolution, we can hardly expect to get things right first time, every time. Some approaches will work well, some won’t, others will need tweaking and turn out to be useful tools down the road in future iterations. Learning from past experience to make the next wave better and more effective is an important part of this process rather than putting everything in one basket and then abandoning it if it doesn’t work first time.

One man who has experienced the first and second waves and is ideally placed to candidly discuss the learnings and future changes needed is Dr Dan Chen. He was global head of cancer immunotherapy while at Genentech/Roche and is now spearheading clinical development at IGM Biosciences, a biotech focused on next generation antibodies and bispecifics.

In order to think about what’s needed in the future rather than rush headlong into a different modality, we first have to take stock and then reflect on the learnings of the past clinical trial experiences in order to figure out how to fix them…

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mRNA – the language of life

It’s time for an extended update on the neoantigen space now that we have new clinical data to look at and discuss. There are a variety of approaches being evaluated in the clinic now, from adenoviral vectors to cell therapies to vaccines.

Indeed, we haven’t covered Moderna Therapeutics before as they were rather quiet in preclinical mode, but now they have some initial clinical data in cancer patients, we thought it would be nice to explore the company’s progress, as well as look at where they’re headed with their mRNA platform.

In the hotseat today, we take a look at the latest developments in the neoantigen vaccine field in terms of oncology settings and have an engaging company interview in the spotlight as well.

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Waves and waves of T cells

NKTR-214 Cover on Cancer Discovery

In the third part of our mini-series on cytokines, we get down and dirty with another pegylated IL-2 approach, this time from Nektar Therapeutics, including an interview with the PI, Dr Adi Diab from MD Anderson Cancer Centre and CSO, Dr Jonathan Zalevsky.

We’ve certainly had many full ranging discussions and chats with the good gentlemen; here we continue our journey to understand more about the science and underlying biology, as well as key biomarkers of response.

We can also be provocative too and put them on the spot regarding their critics and some of the pointed questions that get bandied about, which certainly makes for interesting reading.  Are they justified?

What should we be looking for when analysing the data?  You can find out for yourselves in the latest expert interview.

Other pertinent topics are also covered including where they’re headed and future data readouts to expect.

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Navigating new opportunities in the IL-2 space

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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How failure allows us to continually innovate

After writing about how the design aspects of antibodies can affect clinical performance recently, a few fascinated readers wrote in asking if there were more examples they could learn from.

Sure there are, and so that simple question inspired five more examples.

They range from small to large biotech/pharma, both public and private – no one has dominance in innovation chops, after all.

In this latest review we look at examples from CAR-T cell therapies, antibodies, immunocytokines and even bispecifics – there’s a lot of cool science going under the hood that many casual observers simply do not realise.

What’s more, some of the selected improvements and changes may (or may not) lead to enhancement of clinical performance down the road, so it is important to pay attention to what’s going on relative to each niche rather than be surprised and caught unaware…

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Key highlights on lymphomas from iCML

Lugano: This post offers a rundown and synopsis of a wide variety of lymphoma trials across different subsets coming out of the 15th International Conference on Malignant Lymphoma (iCML) being in Lugano, Switzerland this week.

Lugano is a glorious place to hold a meeting!

The meeting is held every two years on odd years, usually after the EHA conference.

As such, this review may well turn out to be a useful reference point for later offering background and context for the upcoming ASH meeting in December, since there will likely be additional trial updates and readouts in Orlando.

Some of the updates on the early phase 1/2 trials reference preclinical posters from old AACR meetings circa 2012–2014, which is why the Gems from the Poster Hall series can often turn out to be useful predictors of later clinical trials performance!

There’s a lot to cover and discuss this year and some intriguing developments under the radar…

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Alternative approaches to targeting cytokines

We’ve been covering cytokines and chemokines for several years now before they were hot cakes in the oncology space.

Fighting a way through the poster scrums or mosh pit is art in itself!

With a raft of new companies emerging in this area to challenge established players, things are getting much more interesting of late. That means it’s time for a new mini series exploring these opportunities through the eyes of the CEOs and CSOs.

We ask what’s different about their approaches and look at why should you be paying attention to them.

We begin with the first of a new three part series exploring novel and intriguing ways to activate cytokines and stimulate the immune system in various cancers.

This story begins with some new Gems from the Poster Halls that readers may well find fascinating…

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The value of biomarkers in rescuing oncology R&D

Amsterdam – this weekend it’s time to showcase some important updates in hematology from the European Hematology Association (EHA).

It’s really hard not to like continental Europe when you see scenes like this from a major conference:

T cell lymphomas is not a topic we cover very often but it looks like it will receive attention here three times in a month with news from Corvus at ASCO and now an update on the intriguing story on CXCL12-positive AML and PTCL from Kura Oncology.

We’ve been following the latter story for a while now and after the previous looks at the rationale behind the translational data, it’s now time to explore what happens in clinical practice from their ongoing phase 2 clinical trial…

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What’s new with Corvus Pharma?

Corvus Pharmaceuticals LogoA biotech company we’ve been following for several years – on what has turned out to be a rollercoaster ride so far – is Corvus Pharmaceuticals (NASDAQ: CRVS).

They were pioneers in targeting the adenosine pathway with their adenosine A2A receptor antagonist,  CPI–444, now known as ciforadenant.

So what’s new at Corvus? It turns out quite a lot.

At ASCO 2019, BSB caught up with Richard A Miller MD, Co-Founder, President, and CEO of Corvus Pharmaceuticals to learn more about their progress and importantly, where they’re headed.

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