Biotech Strategy Blog

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

Posts from the ‘Lymphomas’ category

Are new pillars emerging in DLBCL?

It’s time to take a short break from the immunometabolism mini-series and turn our attention to aggressive lymphomas such as diffuse large B cell lymphomas (DLBCL).

This week heralded the latest AACR virtual meeting on Advances in Lymphoma in conjunction with iCML.  There were plenty of science focused talks to listen to and learn from, including new developments in oncogenic targeting.

What if we can learn from what the patients underlying biology can teach us in terms of more rationally designed clinical trials?

We know these are diverse and heterogeneous tumours, but this doesn’t mean we can’t take a more precision medicine approach to treating patients.  What can we learn from early trial readouts and genetic analyses?

It turns out, the answer is quite a bit and more information might be available at the forthcoming ASH meeting, so let’s look at what we can piece together from the available data now…

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In our latest company interview we continue our ongoing AACR series on various protein degraders and how they may be useful in hitting difficult targets where small molecule TKIs have struggled mightily for various reasons, which we discuss in detail.

The protein degraders are what we might call large small molecules – they have a large molecular weight in Dalton terms – yet despite their unwieldy size they do offer a number of distinct benefits, which could potentially lead to improved efficacy, reduced toxicity, and enhanced outcomes in the setting of both cancer and autoimmune disease.  At least this is nice in theory, but what actually happens in practice?

Can we learn from the preclinical rationale and experiments to get a sense of what might happen in the clinic?

Find out more about what one emerging young biotech are accomplishing on the protein degradation front in both hematologic malignancies and solid tumours…

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A wet gloomy day in San Francisco was brightened up by some small biotech talks

San Francisco – The other day I mentioned that we could expect some cross pollination across several recent conferences and this latest post on Kura Oncology is one such example of that genre.

We’ve been following their story longitudinally for a while now and with a lot suddenly going on, 2020 could well turn out to be an crucial year for the company.

There is no doubt they have been pursuing a very focused precision medicine approach with tipifarnib and executing nicely on that strategy so far, but as more indications and additional pipeline agents move into the clinic do the same principles still apply?

To find out, we interviewed a couple of their senior executives and discussed both current progress as well as where they are headed…

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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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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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Over the last five years we have followed the trials and tribulations of CAR T cell therapies in ALL and aggressive lymphomas as Novartis, Kite, Juno, Cellectis, Unum and others have undertaken the road less travelled towards filing and approval.

The ASH DASH in action!

Now that we have seen the first two CAR T cell approvals in pediatric ALL (Novartis) and aggressive lymphomas (Kite), with tisagenlecleucel widely expected to be the next one in aggressive lymphomas following presentation of the 6-month JULIET data at the recent American Society of Hematology (ASH) meeting in Atlanta, a key question remains to be addressed:

Is there a threat on the horizon that might be potentially used prior to CAR T cell therapy in refractory lymphomas?

We say ‘yes, there is’ and thus it was interesting to see where this approach might go… including discussion with an expert.

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In our latest thought leader interview from the annual meeting of the American Society of Hematology (ASH) Dr John Leonard (Weill Cornell) provides a lesson on how to interpret key lymphoma data such as ECHELON–1, CAR T cells, and other topics at ASH, as well as what he’d like to see more of in lymphoma clinical trials.

In this hard-hitting interview, Dr Leonard reminds us that the media should not be a mere extension of the PR of companies. Instead he offers his real world insights into what may or may not be practice changing, and how we should interpret CAR T cell therapy data.

Dr John Leonard (Weill Cornell)

It’s a must read for anyone with an interest in lymphoma… here’s an excerpt to give you a flavour of the wide ranging discussion:

 

 

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And we’re off on the infamous ASH DASH

Atlanta Centennial Olympic Park

The annual data drop for the American Society of Hematology (ASH) meeting in Atlanta, Georgia is finally here.

Each year we write a series of in-depth previews ahead of the event exploring different aspects of hematologic malignancies in terms of what’s important, what to watch out for, and also key abstracts that may (or may not) have an impact.

This year we kick off the first of our series with a look at aggressive lymphomas and novel therapies in development including CAR T cell therapies, antibodies, ADCs and targeted therapies. There are some surprsies (of course) and also some potentially interesting relationships and consequences to consider.

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As we move from monotherapies to combinations in the immuno-oncology space, we start to see some intriguing ideas being explored from additional checkpoints to vaccines to neoantigens to immune agonists to oncolytic viruses. There are numerous ways to evaluate how to boost or jumpstart more immune cells upfront in the hope of seeing better efficacy.

One way to do this is to better understand the tumour microenvironment.

Wall of people at ASH16 in San Diego

If we know what’s wrong under the hood, we might be better able to make the immune system get going… more gas, faulty starter motor, dead battery, loose wire, broken fan belt? All these things and more might be a problem so you can see that diagnosing the issue up from from basic and translational work might be instructive for clinical trials.

If you don’t know what problem you’re trying to fix or repair then you might as well be throwing mud at the wall. Just as we don’t expect a car mechanic to suggest changing the battery or starter-motor without first diagnosing the issue, so understanding the tumour microenvironment in each different cancer or disease might also be a helpful strategy.

At the recent American Society of Hematology annual meeting (#ASH16), there was a fascinating sceintifc workshop that focused on this very concept – what’s going on under the hood and how do we go about fixing it?

Here we explore these ideas via an interview with a thought leader and specialist in the field. What he had to say was very interesting and candid indeed.

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One of the interesting and exciting parts of major medical meetings such as the ASH annual meeting, held last month in San Diego, is hearing about new compounds in development.

When it comes to the treatment of aggressive lymphomas, there remains a high unmet medical need to improve the response rate to first line treatment, as well as offer better outcomes post relapse.

At #ASH16, we heard more about a novel ADC called polatuzumab vedotin (Genentech/Roche).

Preliminary safety and clinical data for polatuzumab plus obinituzumab in relapsed or refractory Non-Hodgkin Lymphoma (NHL) was presented in an oral session by Dr Tycel Phillips (University of Michigan).

Three posters were also presented showing early data in combination trials in R/R follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL), as well as in first line DLBCL.

To find out more about the potential of this novel ADC, BSB spoke with Dr Michael Wenger, Senior Group Medical Director at Roche Genentech.

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