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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To be successful as a cancer immunotherapy company, you not only have to be science driven (that’s a given) and offer an approach that could make a difference, you also need a vision and the ability to execute ahead of competitors in a fast moving and competitive landscape.
Dr John Beadle
We’re continuing our series on emerging cancer immunotherapy companies with an in-depth look at PsiOxus, and the vision of CEO Dr John Beadle (pictured right) for it to be a world-leading immuno-oncolytic virus company.
PsiOxus is based just outside of Oxford – it’s part of the so-called “golden triangle,” the area between London, Oxford and Cambridge in the South of England that is a driver of UK science and innovation.
The company is located in a nondescript business park 45 minutes by train from Paddington to Didcot Parkway, followed by a taxi or bus ride. You have to want to make the trip from London!
Dr Beadle kindly spoke to BSB about the competitive advantage the PsiOxus oncolytic virus platform offers, their path-to-market strategy and how he sees the company developing in the future.
With clinical data due in 2017, PsiOxus is a cancer immunotherapy company to watch out for.
Part 1 of the interview focuses on the scientific platform and cancer new products in development that are driving the company forward.
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New Orleans, American Queen
After yesterday’s enlightening conversation on novel ways to jumpstart the immune system including OX40, vaccines, and STING with a self-confessed radicalist aka cancer immunologist (Dr Bernard Fox), we now turn to a self-described optimist for an industry perspective on oncology R&D and Part 2 of our anti-OX40 mini-series:
- What ideas and challenges need to be considered in order to develop a new agent against a novel target, alone or in combination with another unapproved agent?
- We know that mouse models and biomarkers aren’t optimal yet, so how do those issues and other factors influence decision making and clinical trial design?
- It’s not so easy as many think – there are way more unknowns than knowns – so how do companies go about tackling them?
- What can we learn from the readouts?
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It’s Day 6 of our Countdown to the AACR 2016 annual meeting in New Orleans. We’re at the halfway, 6 posts written and 6 more to go! Then it will be daily Live blogs from the meeting.
There’s a lot of cancer immunotherapy at AACR this year, so after yesterday’s post on GITR we’re continuing our mini-series with a look at another immune agonist.
Today, we’re moving onto OX40 (CD134) as a novel immuno-target. Regular readers will know that we’ve been following this target for some time.
Immune agonists such as GITR, OX40, CD40, CD27 and 4-1BB help to rev up T cells. As Dr Tom Gajewski (Chicago) told us last year, in an interview published on the blog and excerpted in Episode 6 of the Novel Targets Podcast: Stepping on the Gas:
…there are inhibitory receptors on activated T cells that are involved with shutting immune responses down. There are also activating receptors that help to rev up those T cells. You might question whether you can push an activator and block an inhibitor, and maybe get a good anti-tumor response going as well.
When we drive a car, we both lift our foot off the break and we step on the accelerator. We have really beautiful data in animals that that this is exactly the case, that if you hit one of those strong positive regulators, and block just one of the negative regulators, you can have complete disappearance of the tumors in mice.
Several of those positive agonistic antibodies against costimulatory receptors are in the clinic. One of them is anti-OX40 that a couple of groups have in the clinic. We’re working with Genentech, that has one of those agents in phase I.
What does the OX40 competitive landscape look like?
In those post we’ve provided commentary on some of the new products in development from companies and highlighted a surprising number of abstracts that you’ll want to watch out for at AACR 2016 if you’re on the cancer immunotherapy track.
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There can be no doubt that immuno-oncology is a hot topic in cancer research of late with checkpoint inhibitors, immune agonists, immunocytokines, CAR T cells, TILs, TCRs, not forgetting innate immunotherapies. We’ve written extensively about many of these topics, but what about the companies behind them and their strategies?
One thing subscribers tell us they love reading about here on BSB is not only fireside chats with thought leaders, but also interviews behind the scenes with company personnel, be scientists, clinicians or CSOs.
Recently, we’ve posted some interviews with Roche and Genentech scientists/physicians about their IO platform that were well received. Today, it’s the turn of AstraZeneca and MedImmune, who are also developing checkpoint inhibitors and immune agonists against various cancers.
With the anti-PD1 antibodies i.e. Merck’s pembrlizumab (Keytruda) and BMS’s nivolumab (Opdivo) already approved by the FDA, and Roche/Genentech’s atezolizmuab well on the way to filing in advanced urothelial bladder cancer with the announcement this week that the IMvigor 210 trial in relapsed/refractory disease met its primary endpoint, the big question now remains is what’s happening with the fourth element of the quartet? How well is progress coming along there and what is the main focus we can expect in the near future?
Like most Brits, when AstraZeneca noted back in 2013 that they expect to establish their global R&D hub in Cambridge, I assumed they meant in the Golden Triangle and not Massachusetts. This is a burgeoning area for European biotech research, which is somewhat ironic after the KuDos scientists working on olaparib (Lynparza) moved to Alderley Park in Cheshire with the acquisition and will likely face moving back again!
At ASCO, we had the pleasure of a chat with Dr Rob Iannone, the head of the AstraZeneca Immuno-oncology development program. The company also published a number of interesting abstracts and posters that were on show in Chicago, as well as a burgeoning pipeline in this area beyond their lead compounds, the anti-PDL1 inhibitor, durvalumab (MEDI4736) and tremelimumab (anti-CTLA4).
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