Scrip: industry news and insights
26 Nov 2020
Executive appointments at MyoKardia, Scancell Holdings and Sutro Biopharma
Trying to catch up with peers in both immuno-oncology and NASH, the German pharma has assigned Sapountzis to lead its US business development efforts. At BIO, he outlined his strategy and goals.
Employed by Boehringer Ingelheim GMBH for 12 years, Ioannis Sapountzis recently was entrusted with overseeing the German pharma's business development efforts in the US, with a focus on specialty care. Sapountzis began his career at BI as a researcher – a medicinal chemist by training – he now oversees the vetting of potential deals to advance BI's efforts in oncology, cardiometabolic disorders and other therapeutic areas of focus.
Sapountzis sat down with Scrip to discuss his plans and goals during the BIO 2017 annual conference in San Diego, noting that "I was always a big fan of external innovation." That outlook and his research background should help the family-owned firm do some catching up in at least a pair of therapeutic areas where BI wants to focus but trails its big pharma peers – immuno-oncology and non-alcoholic steatohepatitis. (Also see "BIO Notebook, Day 1: Janssen, Boehringer And More Talk Deals, Pipeline Progress And Investment" - Scrip, 20 Jun, 2017.)
One strategy the company is trying is a recent decision to split up cancer R&D, with a US-based effort focusing on immunotherapy alongside continued work on targeted therapies in Vienna. Sapountzis outlined this effort, as well as BI's strategy in NASH and its Research Beyond Borders initiative, in a wide-ranging interview.
A: Absolutely. Having a fundamental understanding of what BI is looking for is, of course, important to make successful partnerships and find the right opportunities for us. BI has an equal interest in small molecules and large molecules, so my time working across therapeutic areas and getting to know more about the large molecules side was very important and informative for me. But I think it's good to know how a molecule is progressing within BI's research and development organization to find the right partnerships outside.
We're a little bit agnostic to modalities, to be honest. We do what we have to do, evidenced by our recent investments into mRNA vaccines or oncolytic viruses, so we go where the science goes. [BI signed a collaboration with ViraTherapeutics GMBH last September, including an option to buy the biotech, focused on vesicular stomatitis virus glycoprotein approaches to solid tumors.] (Also see "Boehringer Gets Option To Buy ViraTherapeutics And Cancer Virus Therapy" - Scrip, 28 Sep, 2016.)
I have to admit that our current pipeline is still heavy on small molecules – a bit more than half of our pipeline across the organization is small molecules, but we are moving very rapidly into advancing large molecules and other new modalities in our pipeline.
We also now have our first large molecule, which is Praxbind (idarucizumab) for reversing [the anticoagulant effects of] dabigatran, brought to market and there is more to come. (Also see "BI's Praxbind US Approval May Boost Pradaxa Sales" - Scrip, 16 Oct, 2015.) [The imbalance between large and small molecules] is something that we are aware of but it's not on purpose. It's just in the past we had concentrated more on small molecules but there is an agnostic approach to modality at BI.
A: Our cancer immunology is anchored in four different pillars: oncolytic viruses and cancer vaccines, T-cell engagers and immune regulatory receptors. One thing that is unique to BI, I would say, is that we have built a platform addressing immune regulatory receptors in a more holistic way by not tying them to either oncologic applications or immunologic applications but by looking at the fundamental principles of science that drive immune responses. Then we can incubate [promising leads] either in an oncology set-up or an immunology set-up, so looking at the seesaw of whether you want to suppress or activate the immune system really drives that.
That was something that we established two years ago across research sites and functions – driving the fundamental understanding of immune modulation – and we continue to grow this area and invest heavily into it. This is driven primarily by our research site in Richfield, Conn., [which is working] to capture the benefit of working together with our immunology research center and cancer immunology and drive this. I think that's unique to BI. Of course, everybody is looking at those principles and everybody wants to make an impact and find the next important piece.
I think it's due to our long-term vision and our long-term focus, which allows BI to not look for the quick win but to try to understand the science and basic principles and then go after almost antigen discovery and new target discovery through a couple of our partnerships. Two are in very early work. One is with Eureka Therapeutics Inc., which we entered two years ago, and the newer one is with AbeXXa Biologics Inc., which is looking into MHC [major histocompatibility complex] proteins. We hope to use discovery of these peptides to drive new drugs forward that could be important for immune regulatory principles.
This is only possible if you have a long-term focus, because we go into these collaborations very early, trying to understand the fundamental principles and then drive the work – we're talking about things that are a couple of years away from candidate nomination. I think this is unique to BI, this long-term view that we have, and hopefully it will pan out as a success in the future.
A: While the PD-1 inhibitors and the like have made a great success in non-small cell lung cancer, we think there are still opportunities to improve [on those gains]. We also have a very important and strategic focus to tackle KRAS, which is something that has high prevalence in lung cancer, higher in pancreatic, but very high prevalence of more than 15% in lung cancer. This is an area where the checkpoint inhibitors have not been so successful at this point in time. (Also see "Boehringer’s Oncology Strategy: Build From Niche Lung Cancer Base" - Scrip, 10 Aug, 2016.)
In general, I think the GI tract as such has been a bit underserved. Cancer immunotherapies have not been as successful [there] as in melanoma or in lung cancer. So that's a focus of ours. I think what is also important is that we take a holistic approach and continue to focus on both, not only on cancer immunology but also on cancer cell-directed therapies. And we believe that combining the understanding of both will actually provide a benefit to patients long-term, because you may not be able to address it [solely] with one or the other. You may need to go into combinations of targeted therapies and immune therapies to unlock the potential of the drugs.
We made a conscious decision last year to strengthen our cancer immunology research activities by splitting up the activities in early research between cancer cell-directed therapies and immune cell-directed therapies just to increase the emphasis on each. Cancer immunotherapy work is going to be driven primarily out of our Richfield research site in the US, while our cancer cell-directed efforts are anchored at our research site in Vienna, and will continue to grow there. Of course, we are a truly global organization so there are clinical development synergies with our site in Biberach, Germany, but those are the two main research hubs.
Unlike other large pharma companies, we have made a conscious decision, while separating them on the research side, to keep them together on therapeutic area side. So we have one oncology therapeutic area, which is fed by both of these different research teams.
A: First of all, I think the game is still really open and that's what we firmly believe. There are several underlying principles for fibrotic diseases that we try to understand and I would say that Boehringer is actually ahead of the game there with nintedanib (Ofev) being one of two drugs that were actually approved for idiopathic pulmonary fibrosis. (Also see "Boehringer's Ofev, Roche's Esbriet win same-day IPF approvals" - Scrip, 16 Oct, 2014.)
IPF is very similar to NASH [in terms of] underlying principles. We think we very much understand the underlying principles of fibrosis and can make an impact there to the benefit of patients. That being said, similar to what we did in the field of immune modulation, we have a fibrosis cluster which is looking across therapeutic areas into underlying principles of fibrosis [looking for areas] where we could then further develop them into meaningful medications for patients, whether in NASH or lung fibrosis. Even oncology in part is fibrosis-driven.
So, while we are not ahead of the game in the NASH field, definitely [there is] very much [still] to know about fibrosis. In NASH, in order to make an impact quicker for patients, we took a partnering approach two years ago. NASH is a strategic priority for us, so we partnered with a company called Pharmaxis Ltd. and brought that molecule [BI 1467335, an inhibitor of semicarbazide-sensitive amine oxidase, also known as vascular adhesion protein-1] into the clinic together. Now, we are about to start a Phase II trial with this molecule very shortly.
[This target] definitely is implicated in fibrotic disease. We found this oxidase target particularly interesting and promising in that indication. Our scientists have been very engaged to try to screen the field not only of what is available, but also to come up with a differentiated plan for the development of this program.
A: I like to call it our off-strategy strategy. We go for something that is outside of our strategic focus but make it a strategic priority. While we are so focused on bringing things forward for our core therapeutic areas – respiratory disease, immunology, cardiometabolic, oncology and CNS diseases – we tend to neglect areas that could become the next therapeutic area or the next big wave.
We started with RBB, [marshaling] resources and giving them the clear mandate to go for something that is outside of our therapeutic areas and a couple of core themes to work on. Over three years, they've been growing a global network across hot spots and also utilizing internal resources to grow the science and the understanding of those four [areas of focus] they have been assigned by BI – regenerative medicine, gastrointestinal therapy, the microbiome and hearing loss. Those are the four areas in which RBB primarily is looking for interesting projects and we think that all of them can be very important in the future and may or may not deliver into BI's pipeline.
We are co-located with these colleagues so there is a very good exchange and fruitful collaboration across RBB, business development and also our venture fund.
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