Biotech Strategy Blog

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

Posts tagged ‘Pharma CI’

After yesterday’s popular update on Ignyta where we posted our recent interview with the CEO, Dr Jonathan Lim prior to the 2Q conference call, a flood of questions have come in from eager beaver BSB readers.

Rather than add to an already lengthy article, this seemed a good opportunity to start afresh and do our latest Reader Q&A mailbag on a specific topic, namely the TRK/ROS1/ALK space.

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Tropomyosin receptor kinase (TRK) inhibitors are not a name that rolls off the tongue easily and yet this niche is attracting a lot of interest from observers curious to learn more about a highly targeted approach to rare oncogenes such as TRK, ROS1 and ALK that occur in several different tumour types.

Much of the focus has been on the more commonly expressed ALK-positive lung cancers with crizotinib, ceritinib, alectinib, brigatinib, lorlatinib and others. Crizotinib also targets ROS1 and is approved by the FDA in metastatic NSCLC whose tumors are ROS1-positive.

As the next part of the development in this sphere, TRK and ROS1 mutations are now in the spotlight. Indeed, we have been reporting on the data since 2014, which has been encouraging thus far, particularly from two companies, namely Ignyta and Loxo Oncology.  These two agents differ in that entrectinib targets TRK/ROS1/ALK whereas larotrectinib is a specific pan TRK inhibitor.

There was a new raft of data at the recent AACR annual meeting and more data is expected at the forthcoming ASCO conference.

Here, we take a look under the hood through the lens of one of the small biotechs in this space via a candid interview with Ignyta CEO, Dr Jonathan Lim.

Dr Jonathan Lim, CEO Ignyta

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Over the years we’ve interviewed folks from numerous pharma and biotech companies here on BSB, including those with targeted therapies (small and large), as well as immunotherapies.

Some companies have small pipelines and may be forced by circumstances to explore what they have or seek collaborations with bigger partners.

For big pharmas with large pockets plus broad and deeper pipelines, the challenge is quite different – how do you prioritise potential combinations and tumour targets given it is impossible to evaluate them all in the clinic? How do you create differential advantage and value when you’re relatively later to market compared to your competitors?

In the BSB spotlight this week we have two researchers in clinical development and R&D from the same company, who happen to have both elements in their pipeline in areas of high competition.

Part one of our latest mini-series explores the IO side of the business as we look ‘Through the Keyhole’ at what’s going on in terms of biomarkers, monotherapy trials, combination studies (both IO-IO and IO-targeted) and what to expect in the near-term future later this year. It’s a wide ranging, candid, and fascinating discussion that highlights a lot of potential in terms of what could happen with a large pipeline.

In all, it makes for rather interesting reading and certainly changed how I perceived the company’s efforts in the IO sphere (for the better, I might add).  So what’s fascinating about their approach and what can we learn from their progress to date?

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At the AACR 2017 annual meeting, there was a surprising amount of early clinical data on offer, particularly in the field of cancer immunotherapy.

A shortage of reliable preclinical models that predict human response to cancer immunotherapy has led to a mad rush to the clinic to do trials in man – thee are now over 800 combination trials – if anyone wants to try and follow them all!

If you missed it do listen to the Of Mice and Men” episode of the Novel Targets Podcast recorded at AACR 2016 that features experts such as Dr Bernard Fox (@BernardAFox) and Professor Cornelius “Kees” Melief (Leiden) who discuss the challenges of mouse models.

Several thought leaders at this year’s AACR annual meting described it as “mini ASCO” given the focus on clinical data, with several plenary sessions devoted to the results of early trials.

Dr Julie Brahmer at AACR17 in Washington DC

At AACR17, Dr Julie Brahmer, a leading lung cancer expert and an Associate Professor of Oncology at the Johns Hopkins Bloomberg Kimmel Institute presented long-term survival data for nivolumab in second-line non-small cell lung cancer (NSCLC).

The 5-year survival rate of 16% with a single agent checkpoint inhibitor, while better than historical data with chemotherapy (~4%), is far from being a home-run, illustrating what a dismal disease this is to treat.

One of the challenges that we are starting to see with checkpoint inhibitor cancer immunotherapy is immune escape or acquired resistance in some patients. They may have an objective or partial response, and then relapse and progress (acquired resistance), or they may not respond at all (primary resistance).

From our experience with targeted therapies, it should perhaps come as no surprise that cancers may evolve, adapt and seek to evade immune detection. There are also many inhibitory factors in the tumour microenvironment to overcome in order to enable an immune response.

At AACR17, Dr Brahmer kindly spoke to BSB about what researchers at Johns Hopkins have learnt about checkpoint inhibitor resistance in lung cancer so far. Her insights are both insightful and very useful when we consider what to watch out for at the forthcoming ASCO meeting.

This post is part of our on-going series of expert interviews from AACR17.

In the additional commentary, now that the ASCO17 abstract titles are publicly available, we’ve also highlighted a few that caught our attention.  This is the first in our series of previews of ASCO17. We’ll be rolling out more hybrid posts as we segue our coverage from AACR17 to ASCO17.

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Long time attendees at the annual meeting of the American Association for Cancer Research (AACR) know that there are usually interesting posters and sessions buried on the last day of the meeting.

This year was no exception, with a major symposium on CAR T Cell Cancer Immunotherapy chaired by Michael Jensen MD (pictured right).

BSB readers will recall we interviewed him at the 2016 BMT Tandem meeting in Honolulu (See post: Optimizing CD19 CAR T cell therapy).  Excerpts from this interview also featured in Episode 14 – Cell Therapy Pioneers of the Novel Targets Podcast.

The CAR T symposium on the last day of AACR was one of my highlights of the meeting. The three speakers were:

  • Michael Jensen, MD (Seattle Children’s) Engineering Next Generation CAR T cells using Synthetic Biology-Inspired Technologies
  • Terry J. Fry, MD (National Cancer Institute) Defining and overcoming limitations of CD19 CAR immunotherapy in pediatric ALL
  • Christine E. Brown, PhD (City of Hope) Progress and Challenge in CAR T Cell Therapy for Brain Tumors

Each of these presentations would merit a full blog post in their own right, but in this particular post we’re focusing on CAR T cell therapy targeting glioblastoma multiforme (GBM).

GBM is the most common primary malignant brain tumor, and one with a dismal prognosis – the 5-year survival rate is only around 5%, so there is also a high unmet medical need for new effective treatment options. This devastating disease has proven to be a miserable graveyard for Pharma over the last decade, with many agents unfortunately ending up in dog drug heaven.

After her AACR17 presentation, Dr Brown kindly spoke to BSB.

This post is part of our series of thouight leader interviews from AACR17. It also continues our ongoing posts on the adoptive cellular therapy landscape, and in particular, CAR modified T cells.

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The majority of patients do not respond to cancer immunotherapy. That’s a fact. If you don’t have an immune response to start with, there’s no point giving a checkpoint inhibitor on its own because there are no T cells present in the tumor.

Dr Bernie Fox (@BernardAFox), a world leading cancer immunotherapy expert from Earle Chiles Research Institute in Portland, nailed this a year ago on the Novel Targets Podcast:

“What I teach the first year medical students is that if you have metastatic cancer, the only thing that makes a difference in your life is whether you’ve got your immune system turned on. If it’s not turned on, it doesn’t make a difference what you get, chemo, radiation, surgery, you aren’t going to do well.”

Lincoln Memorial, Washington DC

As we have seen with targeted therapies, drugs can also stop working as a result of acquired resistance. This is also true with cancer immunotherapy treatment.  Cancer constantly evolves and finds ways to bypass or evade detection or ways to kill it.

Faced with a complex jigsaw where we only have some of the pieces in place and an evil double sided version as a model for sneaky advanced cancers, where are we in overcoming cancer immunotherapy resistance?

At the recent AACR annual meeting we spoke with a rising star – an up and coming thought leader in the field of cancer immunotherapy who has taken all the disparate information out there and come up with a perspective on where the field is at and where it needs to go.

Jason Luke MD FACP (@jasonlukemd) is an Assistant Professor at the University of Chicago where, as a medical oncologist, he leads multiple early stage cancer immunotherapy drug development trials and treats patients with melanoma.

Dr Jason Luke AACR17

Working with colleagues such as Dr Tom Gajewski, he has a unique perspective on cancer immunotherapy resistance, and how to overcome this. Dr Luke kindly spoke to BSB in Washington DC.

This is the 3rd post in our series of expert interviews from AACR17.

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Dr Daniel Chen, Roche/Genentech at AACR17

Dr Daniel Chen in the Meet the Expert session at AACR17

At the recent annual meeting of the American Association for Cancer Research (AACR17) one of the 7am “Meet the Expert” sessions was with Dr Daniel Chen.

Chen is a medical oncologist and immunologist. He’s also Vice President, Global Head of Cancer Immunotherapy at Genentech and Roche.

He’s perhaps best known in the cancer immunotherapy field for his publication on the Cancer Immunity Cycle with fellow Genentech VP, Dr Ira Mellman. They have a new publication out on the Cancer-Immune Set Point that takes this forward. (See post: Understanding the Cancer-Immune Set Point).

If you missed it, do listen to Chen & Mellman on Episode 11 of the Novel Targets Podcast recorded in New Orleans during the 2016 AACR annual meeting.

At AACR17, Dr Chen kindly spoke to BSB about his vision for cancer immunotherapy. Anyone who has seen the film, “Jerry Maguire” starring Tom Cruise will remember the moment when Jerry drafts the memo on “The future of our business.”

What does the future of cancer immunotherapy look like from the perspective of a leading industry professional active in the field?

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AACR17 audience

AACR17 audience in Washington DC

Over the last few years we’ve written a tremendous about primary and acquired resistance, both in oncogenic and immunotherapies, as well as on combination strategies for turning non-responders into responders and overcoming acquired resistance that induces clinical relapse.

These concepts were still on display in Washington DC at the 2017 annual meeting for American Association for Cancer Research (AACR), but beyond those obvious top line points, what are the next round of ideas and tools that cancer researchers are focusing on?

Based on numerous presentations, ad hoc discussions, as well as over a dozen one to one interviews we completed with oncology thought leaders, some useful and encouraging trends emerged.

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Prof Peter Schmid

Prof Peter Schmid, Barts Cancer Institute

Peter Schmid FRCP, MD, PhD is Professor of Cancer Medicine at Barts Cancer Institute in London, where he is also Clinical Director of the St. Bartholomew’s Breast Cancer Centre and leads the cancer immunotherapy group.

One of my favourite interview quotes of all time comes from his fellow Barts cancer researcher, Professor Tom Powles who told BSB about the results he had seen with the anti PD-L1 monoclonal antibody, atezolizumab (Roche/Genentech) in urothelial bladder cancer:

“I have a cohort of men and women now, who had been told they have 6 months to live who are now two or three years down the line.”

This encapsulates the hope that cancer immunotherapy offers. (See post: Atezolizumab PDL1 Checkpoint Inhibitor will change Bladder Cancer Treatment).  You can also hear Prof Powles on the Novel Targets Podcast (Episode 7).

Barts Cancer Institute in the City of London is pioneering research into cancer immunotherapy in both the clinical and preclinical arenas.

Readers may recall we previously interviewed Professor Fran Balkwill last year about the work her research group is doing into modelling the tumour microenvironment. This is an exciting area that we can expect to hear more about. (See post: Modelling the Tumor Microenvironment).

So where are we with breast cancer immunotherapy in triple negative breast cancer (TNBC)?

It’s now two years since the first atezolizumab TNBC clinical trial data was presented by Dr Leisha Emens (Johns Hopkins) at the 2015 annual meeting of the American Association for Cancer Research (AACR), how time flies!  (See post: Checkpoint Inhibitor Data Rocks AACR 2015)

As regular readers know, we like to follow stories over time and report on how the longitudinal data progresses.

Professor Peter Schmid kindly spoke to BSB at the 2017 AACR annual meeting in Washington DC where he presented more mature clinical trial data for the PD-L1 checkpoint inhibitor, atezolizumab, as a single agent in TNBC.

What are the key take homes from this data, and the ongoing challenges and opportunities in TNBC?  Prof Schmid shared his unique perspective.

This is the first in a series of expert interviews from #AACR17.

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Washington DC – this is our final daily post from the 2017 annual meeting of the American Association for Cancer Research (AACR).

Starting on Monday we’ll be writing up expert interviews and providing commentary and analysis around some of the sessions we went to and the data we heard.

Tuesday at AACR17 was a day when the Corvus Pharmaceuticals stock dropped 50% following presentation of preliminary clinical data for their A2A receptor antagonist CPI-444.

It’s hard not to be disappointed when you see the waterfall plots skewed to the left and above the X axis, but we really don’t have enough data yet to determine whether CPI-444 on it’s own or in combination with atezolizumab may offer benefit to some cancer patients and if so, which ones.

The company have expanded the renal (RCC) and lung cohorts (NSCLC) in their initial trial, and they’ve told us to expect more data at ASCO17 in a few weeks time. Small cap biotech stocks can be a roller coaster when it comes to data presentations at major medical/scientific meetings.

What else caught our attention in the sessions we attended on Tuesday at #AACR17?

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