Biotech Strategy Blog

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

Posts tagged ‘SITC 2018’

The challenges of bispecifics

We tend to think of the Fall cancer conference season as full of hope for new molecules showcasing encouraging yet early new data.  Rarely does negative data or unexpected trial glitches immediately jump to mind, although it unfortunately happens with startling regularity!

We’ve received a few enquiries and questions about an update on the Macrogenics platform recently.

The company have what they call a Dual-Affinity Re-Targeting (DART) program that includes bispecifics, mostly with CD3 as a standard co-stimulatory domain, although some are dual inhibitory checkpoints instead.

After writing about rather modest clinical efficacy with enoblituzumab monotherapy (anti-B7-H3 antibody) at the SITC 2015 meeting, I suspect that few of the attendees were envisioning an unexpected side swipe after this year’s event with one of their bispecific molecules, but so it came to pass.

As always, there’s a lot more to the central issue of ‘raised liver enzymes’ than meets the eye, so by popular reader request we walked through the issues and evidence to take a look at what’s behind this phenomenon…

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What can we learn from early IO trials?

SITC Phase 1 Review Part 1 – It’s time for a two-part mini-series on recent phase 1 clinical trials and how to interpret the findings.

Are we at a crosswords with IO combos?

As a former new products development professional, this is something that I’m particularly enthusiastic about.

While it is fascinating to see other people’s reactions to early oncology trials, these should often be taken with a very large pinch of salt, in my view.

In Part 1, it’s time to take a step back and understand not only what companies are doing, but also how they set the trials up and what they are looking for. We highlight some examples of data readouts to illustrate the points.

In Part 2 on Monday we take a rock around the clock at some of the other recent phase 1 readouts and explain what we can learn from what was presented. The devil is often in the small details that many observers miss at first glance.

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Pinning down potential new opportunities for IL–8 and 4–1BB

The keynote address at the 2018 CRI CIMT EATI AACR International Cancer Immunotherapy Conference in New York last month was given by Ignacio Melero (Pamplona). Professor Melero gave an engaging and informative presentation entitled, “The immunotherapy faces of Interleukin–8 and CD137.” He also had a related talk on “4–1BB and Metabolism” at the Society for Immunotherapy of Cancer (SITC) meeting this weekend.

Pinning down new opportunities in IL-8 and 4-1BB

The late and sadly missed, Dr Holbrook Kohrt (Stanford), worked closely with Prof Melero on targeting CD137 or 4–1BB, as it’s more commonly known.

Regular readers may recall our interview wth Dr Kohrt back at Immunology 2015 in New Orleans (Link).

If you missed it, we also shared some excerpts from this discussion on Episode 6 of the Novel Targets Podcast, “Stepping on the Gas” (Link). There was also a tribute to Dr Kohrt from Dr Ron Levy (Stanford) at the start of Episode 11 of the podcast (Link).

Professor Melero kindly spoke to BSB at SITC 2018 and shared his thoughts on where we are three years on and where his research is currently focused in relation to cytokines, and in particular, IL–8.

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An analysis of Nektar’s latest PIVOT data and pipeline update

Dr Adi Diab (MD Anderson) at SITC18

Washington DC – At the Society for Immunotherapy of Cancer (SITC) meeting on Friday evening, Dr Adi Diab (right) presented an update on the NKTR–214 plus nivolumab data from the phase 1b/2 dose escalation and RP2D expansion trial (PIVOT–02) in patients with 1L metastatic melanoma in the cytokine session chaired by Dr James Gulley (NCI) and Dr Darrell Irving (MIT).

Nektar also held an investor meeting over the weekend to discuss the data as well as where they are headed with their early pipeline compounds.

As we seek to find new and effective partners to add to immune checkpoint blockade, there are going to be some hits and misses in the mix.  This year alone April turned out to be a pivotal month in the calendar, as chemotherapy plus pembrolizumab was a big hit in 1L NSCLC from the KEYNOTE-189 trial at AACR, while Incyte’s IDO inhibitor, epacadostat, bombed as 1L treatment of unresectable or metastatic melanoma in the phase 3 ECHO-301 study.

Cytokines have definitely garnered a lot of interest of late, with some very creative molecules now emerging to address the systemic toxicities associated with traditional approaches. We’ve been covering the Nektar pegylation story for several years now with numerous updates, so how are the data looking this time around?

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How the microbiota impact response to cancer immunotherapy

We’ve been eagerly following the story of the microbiome and how it affects the response of people undergoing an allogeneic transplant or cancer immunotherapy since Marcel van den Brink’s original presentation at SITC in 2014, followed by Tom Gajewski the following year.

Since then, it has been fascinating to watch how the commensal microbiota has evolved into a niche unto itself. It’s one thing to report differences academically, but clinically we want to know if the information gleaned can help impact patient care. van den Brink’s group demonstrated that both GvHD and antibiotics could influence outcomes in their patients undergoing a stem cell transplant for hematologic malignancies and limiting use of ‘bad antiobiotics’ could change the course of outcomes.

A packed Microbiome session at SITC 2018

The Chicago angle was quite different. They noticed differences in the microbiota of their lab mice could impact the responses of their experiments with immunotherapy. Could that also impact patients? The answer was yes and off they went on a journey probably none of them anticipated to look at responders and non-responders in their melanoma cohort.

That then begs the question of whether the microbiota can be influenced and the outcome changed?

Several other groups of relevance in this space are the Laurence Zitvogel and Guido Kroemer labs in Paris, as well as Jennifer Wargo’s lab at MD Anderson in Houston.

We continue following the microbiome story to learn where we are and where we are going…

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New developments in immune escape

DC sculpture

Up on deck today we have some highlights from my notes from SITC18 session on Immune Escape: Current Understanding of Mechanisms and Advances in Therapeutics Approaches held on November 7th, 2018.

This is a topic that I find particularly fascinating, not least because it has distinct parallels with what we have learned from chemotherapy and targeted therapies over the last couple of decades, so why not immunotherapy too?

Semantically, I’m not hung up on terminology either – call it resistance or immune escape, the negative effect on therapy is what matters and even some of the mechanisms are similar, such as the development of JAK mutations, for example.

The important point there was plenty to think about and consider in terms of what the data tell us from the patient tumour analyses and where they might direct us in terms of future research as well as novel combination approaches.

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SITC18 Preview and IO curiosities

SITC18 is in Washington DC

The SITC abstract titles have now dropped on the very same day as the ASH abstracts (handy timing for those who revel in data tsunamis!) although the actual details of the abstracts won’t be available until Nov 6th.

In this latest conference Preview, we take at look at the titles and have selected some for commentary based on what we know, and in some cases, what we might expect.

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The Potential for Cytokines in Cancer Immunotherapy

The potential of cytokines in cancer immunotherapy is now attracting a lot of attention with many in industry assessing whether they need a cytokine in their pipeline and if so which one may make the optimal combination partner.

We’ve been writing about cytokines for several years now and have been following several cytokine molecules, including Nektar’s novel pegylated IL–2 (NKTR–214) approach and Armo’s pegylated IL–10 (AM0010). Other technologies in early development include an IL–8 agonist from BMS and an IL–15 superagonist fusion protein from Altor Bioesciences.

#ASCO18 Blisterwalk to Developmental Therapeutic sessions

What does the future hold for cytokines – are they really the “best thing since sliced bread,” as we say in England or will they fizzle out and not prove to induce additive effects over and above monotherapy with checkpoint blockade?

For a view of where the field is at and where it might be going, while in Chicago at ASCO 2018 we spoke with Dr Mario Sznol, who is a medical oncologist at Yale Cancer Center in New Haven, where he treats melanoma and kidney cancer patients.

He’s one of the leading translational researchers in cytokine drug development and is also the in-coming president of the Society for Immunotherapy of Cancer (SITC).

Readers of Biotech Strategy will recall that we last spoke with Dr Sznol at the 2015 SITC annual meeting where he talked about his renewed interest in cytokines, and in particular, interleukin–2 (IL–2) (See post: Novel immunotherapies and combinations). Since then, much has happened and there are now even more targets being investigated, as well as a wider cadre of researchers actively involved in this field.

Being president of a medical or scientific association takes up a lot of time, so it was a privilege to talk with Dr Sznol again, before he takes up his new honorary position in 2019.

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