Biotech Strategy Blog

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

Posts tagged ‘Genentech’

Not in Chicago: We continue our ASCO coverage with a look at the evolving TIGIT landscape and the initial tiragolumab data in lung cancer.

With all the breathless hype of late one wonders if some observers believe (accompanied by loud trumpeting of horns) this is the next big checkpoint target after CTLA-4 and PD(L)1, but is it?  The field has barely got started with a raft of new trials opening to evaluate several molecules in different combinations across solid tumours, and yet we have something of a fanfare already.

Will TIGIT roar and fire up the immune system in some people with cancer or will it fizzle out?

To those of us familiar with new product development and early stage development the ‘hot’ status is likely leaving us somewhat bemused at the noise around the emerging targets, after all it’s going to be a long while before we see those all important phase 3 readouts with appropriate head-to-head comparisons.

In this latest article, we take a look at the Genentech antibody, tiragolumab, and also discuss the development with a company executive to gain their perspectives, insights and rationale on what was behind the recent trial expansions beyond the phase 1 study in advanced solid cancers.

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Continuing our ASCO20 coverage with another Preview in the pre-meeting series, we turn our attention to a particular modality of keen interest to many of our readers.

In this latest article, we highlight ten areas within the niche and include an array of companies, both big and small, across Pharma and Biotechs.

Some of them have some nice data to share, others will be footnotes to the meeting, but who fits into what category and what can we learn from the abstracts upfront?

To find out more, we looked very carefully at the hints and nuance which inevitably grace the writer’s pen – it’s time to hone in on where are the flourishes and the crossings out this year?

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Time for some additional colour commentary!

There has been some incredibly intense interest surrounding TIGIT as a new therapeutic target in oncology of late, to the point where some observers have been wildly claiming this is the new universal checkpoint everyone has been waiting for.

But is it?

It’s early days yet with little data presented from people with cancer, so at this point it could well be a bit of a stretch to find another anti-PD–1/PD-L1 equivalent, but this doesn’t mean there isn’t utility in seeing clinical activity in some tumour types, far from it.

In our latest post, we take a look at what’s coming up in the TIGIT niche, along with an interview from a company active in this niche.

What do the company have to say and how do they see this panning out?

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Can we break through the barriers of a hostile tumour microenvironment?

Who would have thought that after 30 years of no new therapies that urothelial carcinomas would suddenly be almost constantly in the spotlight with enticing words like cancer immunotherapy, biomarkers, tumour microenvironment, translational immunology etc?

And yet it has happened – with a lot more to come in this highly competitive niche too.

Prior to AACR in Chicago, we highlighted TGFβ in our Preview series as an important emerging target that is gathering attention and may be relevant in tumour types, such as urothelial carcinoma and ovarian cancer.

After the meeting, Dr Paul Rennert (CSO, Aleta Biotherapeutics) noted:

I don’t disagree with either of these sentiments – there was a reason we interviewed a lot of NK cell enthusiasts recently and we have since been rolling out our thought leader mini-series focused on TGFβ. Yesterday, we kicked off with perspectives from an academic researcher active in this field and tomorrow will showcase some practical clinical perspectives.

On deck today, we have a interview with a research scientist who has conducted both basic and translational work for a discussion about how he sees the learnings that have arisen from bench to bedside and back again.

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Chicago!

One of the key topics arising out of probably the hottest session (lung cancer clinical trials plenary) at AACR last week was tumour mutation burden (TMB).

An important question to be addressed was whether or not the nivolumab plus ipilimumab combination from the CheckMate–227 study will be useful in previously untreated non-small cell lung cancer (NSCLC) patients with a high TMB?

There are a number of questions that occurred to us that need careful consideration:

  • Is TMB ready for prime time?
  • What are the challenges and issues involved?
  • How useful are the data from CheckMate–227 and CheckMate–568?
  • Where are we going next?

To find out more, we had some fascination discussions at AACR with two up and coming young researchers from industry (Dr David Fabrizio of Foundation Medicine) and academia (Dr Nicky McGranahan from UCL in London), who are both experts intimately involved in measuring TMB.

What did they had to say and what does it all mean?

Their candid answers may well surprise a few people…

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For what seems the longest time, we have seen the battle in metastatic clear cell renal cell carcinoma (ccRCC) being focused on various anti-VEGF TKIs, whether against interferon, mTOR inhibitors, and even each other.

Lately, anti-PD(L)1 antibodies have also come on the scene – both as monotherapy and in different combinations – so are things set to change?

Will it be plaining sailing or are there hidden dangers ahead for the unwary?

Here, we take a look at the ever evolving landscape in RCC and explore the issues and challenges surrounding some of the novel combination readouts, including a look at the role immuno-oncology might play going forward.

Not surprisingly, there’s a lot to consider, discuss and think about…

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Dr Ira Mellman is a leading cancer researcher, familiar to many in cancer immunotherapy for his work on the Cancer-Immunity Cycle and Cancer-Immune Set-Point with Dr Dan Chen.

Prior to joining Genentech, he spent 20 years as a faculty member at Yale, publishing extensive research on dendritic cells.

River Rhine, Mainz

Last year, Genentech announced a strategic collaboration with Mainz based BioNTech in Germany to develop and manufacture personalized mRNA based cancer vaccines.

At the recent CRI-CIMT-EATI-AACR cancer international cancer immunotherapy conference in Mainz, Dr Mellman kindly spoke to BSB about the underlying biology/immunology, the rationale behind the BioNTech collaboration, and his vision on where he sees the potential for therapeutic cancer vaccines going forward.

This is the second post in our series on the Future of Cancer Vaccines.

Here’s a snippet of the interview with Dr Mellman to get you warmed up…

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Dr Bernie Fox (@BernardAFox) is a man on a mission to #FinishCancer, a Twitter hashtag he uses to reflect his vision.

A cancer immunotherapy rockstar, Bernard A Fox, PhD, is the Harder Family Endowed Chair for Cancer Research at Providence Center Center and Chief of the Laboratory of Molecular and Tumor Immunology at the Earle A. Chiles Research Institute in Portland, Oregon.

Fox is also a past president of the Society for Immunotherapy of Cancer (SITC) and CEO of UbiVac, a biotechnology company focused on therapeutic cancer vaccines.

Readers of the Blog and Novel Targets Podcast listeners will recall we had the privilege to interview Dr Fox back at the American Association for Cancer Research (AACR) annual meeting in New Orleans in 2016: “AACR Cancer Immunotherapy Insights from Dr Bernard Fox.”

Fast forward 18 months… it is now time for a detailed update on this issue, as a few interesting events have since come to light in this niche with Genentech/Roche abandoning development of their OX40 agonist, coupled with several new publications from different labs suggesting that concurrent administration of an anti-OX40 antibody with an anti-PD1 antibody attenuated the effect of anti-OX40 and resulted in poor treatment outcomes in mouse models.

Dr Fox kindly spoke to Biotech Strategy Blog about some of the key learnings from this research, where he sees the future potential for OX40, and what his vision for cancer immunotherapy is.

Here’s a short clip from the fireside chat…

 

He’s definitely a man on a mission to #FinishCancer!

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Back in January this year, we posted an early look on what to expect from the evolving 1L NSCLC landscape following the controversial FDA submission of Merck’s pembrolizumab with chemotherapy. This lead to subsequent approval in May.

Checkpoint Charlie, Berlin July 2017

At that time, quite a few people were shocked and surprised that the phase 2 KEYNOTE–021 Cohort G data presented ESMO was neatly parlayed into accelerated approval in the US.

Since then, a lot has happened and now many readers are on tenterhooks as we await the next round of lung cancer trial results in the upfront setting.

First up is AstraZeneca’s MYSTIC trial exploring an IO-IO combination with durvalumab plus tremelimumab. Merck’s confirmatory trial for pembrolizumab plus chemo is also expected in the fall – will it support the accelarated approval – or not? Meanwhile, we also await Roche/Genentech’s IMpower150 study evaluating their checkpoint inhibitor, atezolizumab, in combination with chemotherapy by the year end.

These are quite different strategies with diverse endpoints so following them closely will be key to understanding what happens next.  Based on what we’ve seen in lung cancer to date, the roller coaster looks set to continue.  The C-suite shenanigans have only added to the intrigue and mystique – do they mean anything?  Who knows, but we’re focusing on the hard data i.e. science and the clinical clues that are available.

It’s all to play for and many readers wrote in asking for an update on the landscape and what to expect now that we’re much nearer to the shoes actually dropping.

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IDO/TDO inhibition is a topic we’ve been following the progress on for several years now with various updates along the way. It’s also one of our most requested Previews for this year’s ASCO meeting taking place next month.

The Bean, Chicago

In Chicago next month, initial data from several trials is due to be presented.

  • What can we expect?
  • How are the main players in this landscape doing?
  • Will this combination be the next big thing in the oncology IO space?

In our latest #ASCO17 Preview, we take a hard look at IDO/TDO inhibitors.

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