This feature is part of a series focused on Alzheimer's disease. To view other posts in the series, check out the spotlight page.
For anyone who has ever watched a grandparent or a parent lose the battle to Alzheimer’s disease, they know how completely devastating it can be to see the ones they love slowly slip away — losing all good memories from their past, gradually forgetting friends and family and even completely forgetting themselves. With a large part of the population aging, more people are going to have to face this unfortunate reality.
The horrifying neurological disorder has puzzled and frustrated scientists for the better part of three decades. While virtually every disease-modifying drug that has been researched has failed, the industry is still surprisingly optimistic. Maybe it’s the large unmet need, or maybe it’s the potential of an uber-blockbuster payout if they succeed. Either way, Alzheimer’s research continues to be strong.
Roche is just one of the many big pharmas exploring treatments. The company has two late-stage assets, as well as a third entering clinical development. Although its lead candidate, crenezumab, showed mixed results in Phase 2, the company has decided to push ahead.
BioPharma Dive caught up with Genentech’s global head of neuroscience and ophthalmology business development to talk about what Roche’s big biotech is doing in the space and how it plans to be best in class. Here’s what Tom Zioncheck had to say:
Editor's Note: The following interview has been condensed and lightly edited for clarity. One section has been updated for further clarification since the original publicaiton of this article.
Beginning with business development
Tom Zioncheck: Let me tell you our story. It’s been a really exciting time for the last, I would say, couple of years — in particular with all of the renewed efforts that are going on in the Alzheimer's disease field. And we have really been, I think, at the forefront of trying to face the challenges of this horrendous disease and rising up to meet this unmet medical need. We're doing that in multiple ways. We have extensive efforts in the anti-A beta antibody space and we also have an anti-tau antibody in development.
The pipeline at Genentech actually got started through business development licensing efforts back in 2006. We partnered with a Swiss company called AC Immune for their anti-A beta program and it was a pre-clinical antibody at the time. Working together, we've moved that antibody through clinical development and its currently in Phase 3.
We have two Phase 3 programs ongoing right now and they’re called CREAD1 and CREAD2. We're very excited about the programs, expecting read-outs as early as 2020. The Roche Group also has another play in Phase 3 called gantenerumab. We obviously are working together under the same Roche Group umbrella, and I think it just goes to show our commitment in this space, by actually making an investment in two different antibodies and two large Phase 3 programs. And so that really allows multiple shots on goal.
Two differentiated approaches
Tom Zioncheck: So the crenezumab antibody is an IgG4 isotype antibody, which has reduced "effector function
." compared to an IgG1 isotype antibody. The hypothesis behind the selection of the IgG4 backbone was that reduced effector function would lower the risk of amyloid-related imaging abnormalities (ARIA), a safety issue that has been seen with several anti-A beta IgG1 antibodies.
Crenezumab antibody was derived through a business development collaboration with AC Immune. That was in 2006. We had a very good experience working with AC Immune, and then did another licensing deal with them in 2012 and collaborated on the anti-tau program.
That was a pre-clinical antibody program that is now in Phase 1. Tau is another, we believe, very important target in Alzheimer's disease, and more recent data correlates with the presence of these tau tangles and fibers. It tracks the presence of cognitive loss better than amyloid beta.
So we are excited that tau may be yet another targeted approach for the treatment of Alzheimer's disease. We think we have the possibility of being best-in-class and first-in-class with the antibody program that we have. All of this is being facilitated with the use of a tau (positron emission tomography) PET probe that was developed at Genentech we call GTP1. And as I'm sure you're well aware, one critical advance in the field has been imaging and biomarkers.
And we think that this tau PET probe being selective and specific for tau is going to allow us to enrich patient populations and hopefully identify those patients that are going to be at the highest probability of responding to the therapy. And the plan will be to make use of the PET probe in our Phase 2 study.
Business development sentiment is changing
Tom Zioncheck: I think that society is now far more aware of the challenges that we face with this disease and are becoming aware of the unmet medical need. So much of the focus over the last decade or two has been in oncology, but now I think pharma, and to a certain extent all of society, is more aware of this devastating disease and the impact it can have, not only on patients but their caregivers.
"People fully realize the high risk nature of developing drugs in Alzheimer's"
Global head of neuroscience and ophthalmology business development
I think that there's a heightened awareness both in society and in pharma about the problem, and people fully realize the high risk nature of developing drugs in Alzheimer's, but in many ways they see a counter-balance by the incredible unmet medical need.
So we are fully invested in trying to find significant cures, treatments for Alzheimer's disease. We're focused on disease modifying therapies, specifically at Roche and Genentech. We're not particularly interested in things that just address symptomatic new treatments.
And our efforts over the last decade have really been on the targets of A-beta and tau. But now with the new technologies, biomarkers, advances in imaging, we're excited by new targets that are starting to emerge. So we're quite excited by the possibility of new advances coming and we're … looking for partners that have exciting new approaches, new therapies, new diagnostic, new biomarkers.