At Bayer’s annual Pharma Media Day on Monday, top pharmaceutical executives trumpeted the company’s R&D progress, starting with its pipeline of about 50 programs, as well as plans to grow into a “top 10” oncology drug developer by 2030.
That growth, according to Bayer, will be driven heavily by the prostate cancer drug Nubeqa® (darolutamide), which Bayer co-developed with Finnish-based Orion. Nubeqa won initial FDA approval in 2019 as a treatment for non-metastatic castration-resistant prostate cancer but is pursuing an additional indication of metastatic hormone-sensitive prostate cancer (mHSPC).
This month, Bayer tripled its peak sales forecast for the oral androgen receptor inhibitor, from €1 billion ($1.1 billion) to €3 billion ($3.4 billion), following positive clinical data presented February 17 at the 2022 American Society of Clinical Oncology (ASCO) GU Cancers Symposium. The data showed that Nubeqa plus androgen deprivation therapy (ADT) and docetaxel reduced the risk of death by more than 30% in patients with mHSPC compared to ADT plus docetaxel. Nubeqa patients also showed a more than double median treatment duration vs non-Nubeqa patients (41.0 months vs. 16.7 months).
Nubeqa is one of several newer drugs Bayer is counting on to recoup sales it expects to lose as several longtime top-selling drugs fall off the patent cliff. Among them are blood thinner Xarelto® (rivaroxaban), co-marketed with Johnson & Johnson; and Eylea® (aflibercept), co-marketed with Regeneron for wet age-related macular degeneration (AMD) and other eye disorders. Last year, Bayer projected a resulting “low- to mid-single digit percentage decline” in 2024 pharma sales, to be followed in 2025 by a return to sustainable growth.
Through launched and more recently development of additional indications, Bayer is also looking to boost sales for the solid tumor drug Vitrakvi®(larotrectinib); cardiovascular drug Verquvo® (vericiguat), co-developed with Merck & Co.; and Kerendia® (finerenone), designed to slow the progression of chronic kidney disease in adults with type 2 diabetes.
The Media Day event capped a busy early 2022 for Bayer, during which the pharma giant:
- Expanded into in vivo gene-editing therapies by committing potentially more than $1 billion to a strategic collaboration and option agreement for Mammoth Biosciences’ CRISPR systems.
- Returned to Evotec rights to eliapixant, under study for indications including refractory chronic cough—where the drug showed positive Phase IIb data in September. Bayer concluded eliapixant’s development risks outweighed benefits.
- Completed treating the first cohort in a Phase I trial (NCT04802733) of subsidiary BlueRock Therapeutics’ pluripotent stem cell-derived dopaminergic neurons in patients with advanced Parkinson’s disease.
“We are currently in the remarkable position to launch several important new medicines in parallel, and are unlocking the full potential of our assets through systematic data generation, multi-indication approaches as well as building on new digital business models,” stated Christian Rommel, Bayer’s Head of Research and Development and a member of the Executive Committee of Bayer’s Pharmaceutical Division.
February marks Rommel’s first anniversary at the helm of Bayer’s R&D efforts, based in Berlin, a nearly six-hour drive from Bayer’s headquarters in Leverkusen, Germany. He joined Bayer from Roche, where he served as Senior Vice President, Global Head of Oncology Research and Early Development based in Roche’s HQ site of Basel, Switzerland. Before Roche, Rommel held executive-level R&D roles at Amgen and Intellikine (acquired by Takeda Pharma), as well as scientific leadership positions at Merck Serono (now Merck KGaA, Darmstadt, Germany, and Regeneron Pharmaceuticals.
Rommel recently discussed Bayer’s approach to R&D and accomplishments with GEN Edge. (This interview has been lightly edited for space and clarity.)
GEN Edge: February marks your one-year anniversary at Bayer as the head of R&D. What have you found most challenging and most rewarding over the past year?
Christian Rommel: It’s been a long year, but exciting! The most challenging aspect has been to change places and onboarding in a new environment during a pandemic. On the other hand, many people made even more effort, and extra effort, to build relationships and make connections.
I feel humbled by the opportunity to join a company with such standing in history as we reinvent R&D at Bayer for the next decade. I’ve come to the realization how much Bayer has transformed itself. Our story is evolving, so I’m really energized by the opportunity I’m being given to participate.
It’s important to remind ourselves, what did I find at Bayer? I could easily connect to a lot of values, and one is the commitment and the focus on patients. So, while we changed a lot of things, everything we do—from new technology to investment—originates from an understanding of human diseases and how we can help patients.
I also found that, besides a lot of talented people, there are a lot of powerful capabilities that are very competitive. Some of them need a bit of a jolt, but nevertheless I’ve seen radiotherapies or radiopharmaceuticals from the platform stemming from partnering with Algeta on [prostate cancer drug] Xofigo®. And we enhanced this by the acquisition of Noria Therapeutics and PSMA Therapeutics in 2021, with the BCMA-targeted actinium-225-labeled small molecule, which hopefully we will put in the clinic this year.
GEN Edge: Over the past year, Bayer has put into motion a new R&D strategy and innovation strategy. What does Bayer aim to accomplish? And where does innovation fit within Bayer right now?
Rommel: When we talk about the legacy, I was deeply impressed… Yet we thought strategically, how can we leverage the strengths there and take it into the next decade? And one example was the combination with Vividion Therapeutics.
Vividion combines proteomics approaches with small-molecule, special library design screening to identify previously unrecognized, untapped pockets in the natural stage of any protein and solution of the human proteome. That provides us a hook into any target of choice. Very often, the team is able to further engineer those molecules to bring a function to the protein, so it inhibits, activates, modulates, and so forth.
We’ve seen an enormous opportunity to combine the strengths, resources and knowledge of a large pharma in this modality in small molecules with innovation and groundbreaking pioneering work, like the work that Benjamin Cravatt [PhD] at Scripps Research has pioneered over many years, which ultimately led to the foundation of Vividion with some of his colleagues.
The combination of these two is a very rare opportunity to create a 1+1=3 formula. It starts with the understanding of human disease biology. Today, with all the genetics, genomics, and information, single-cell sequencing, and so forth, we’re getting to a target space that with conventional ways we cannot address any more, but the opportunities are in front of us.
GEN Edge: What does that target space look like to Bayer?
Rommel: We have to target what the disease biology requests from us to target: the key drivers in cancer, right? Key resistance mechanisms. Many of them have been previously described as still undruggable. I find it incredibly inspirational to say we don’t want to accept the term “undruggable.”
We want to fearlessly go in the space and take on key targets in new ways, and that’s what Vividion brings us. When I came to Bayer, I found this powerhouse of chemistry. Yet there was a need for innovating it. This we accomplished with external innovation in the business deal with Vividion, a bolt-on acquisition.
We’re operating Vividion on this arm’s length concept: this company operates in a very autonomous, independent manner. Vividion is managed by a board, but they’re fully held accountable and fully supported to independently build their science and pipeline, that we will co-develop at some point, of course.
GEN Edge: Another company that Bayer acquired, BlueRock Therapeutics, recently announced closing enrollment in the first of two cohorts in a Phase I trial evaluating dopaminergic neurons—actually replacing the neurons in patients with advanced Parkinson’s. We’ve seen numerous approaches that didn’t work in the clinic. How will Bayer avoid that fate?
Rommel: BlueRock is truly pioneering a new therapeutic approach in this case. BlueRock was a key building step in our long-term strategy of cell and gene therapy. What BlueRock is doing—which almost gives me goosebumps when I talk about it—is taking stem cells and in an experimental environment, engineer them by molecular steps to become so-called authentic neuronal cells—they respond and are able to produce dopamine.
The concept is to bring those cells into patients with advanced Parkinson’s disease, where you have degeneration of neuronal matter. And with this, you lose dopaminergic neurons, or neurons that produce dopamine. We replace them with stem cells—neuronal-derived neuronal cells that are capable of delivering dopamine into the brain.
Cell-based therapy engineering, from stem cells to neuronal cells, is a targeted, highly specialized surgical intervention for patients, implementing the cells at a certain geographic hotspot for Parkinson’s disease. Fingers crossed, we hope, based on groundbreaking preclinical and scientific research from the founders of BlueRock—one of them is Lorenz Studer, MD [scientific co-founder of BlueRock and Director, Center for Stem Cell Biology at Memorial Sloan Kettering Cancer Center], and other well-recognized key opinion leaders in this area. We hope that their work translates into therapeutic outcome.
[In January], we announced with some pride that we closed the first Phase I cohort of seven patients. Now, we have to follow them through, and then arrange to continue enrolling additional patients, eventually with a step up of the cell numbers.
GEN Edge: How does BlueRock reflect Bayer’s renewed commitment to R&D?
Rommel: That is one aspect where we realize how much we’ve changed Bayer in pioneering those new therapeutic approaches and modalities. But I should also mention our other arms-length company AskBio, we are also bringing forward an AAV-based gene therapy that delivers the human glial cell line-derived neurotrophic factor (GDNF) gene. It’s a vector system that produces a neurotrophic growth factor, a neurotrophic factor that may help to manage the fitness and the functionality of neurons to continue to produce dopamine.
In diseases where you have cell loss, replacing cells by cell therapy, or bringing in a gene that hopefully maintains the cellular integrity, function and fitness, makes a lot of sense. With this, we go to the root cause of the disease. And you have two pioneering approaches: gene therapy from AskBio, and cell therapy from BlueRock.
GEN Edge: Bayer has committed to growing a leading cell and gene therapy business. How will you accomplish that? Are the companies that Bayer has acquired the beginning, or will Bayer need to add to those and expand its CGT pipeline?
Rommel: First, what is leadership? Leadership, I think, is when you take the first step, you go from zero to one, right? You’re really a pioneer. With stem cell-derived neuronal cell therapy and Parkinson’s, as BlueRock does, all our colleagues from AskBio see this as leadership.
Second, leadership is having the integrity in being an expert and being highly regarded. I think the founders and the management of AskBio and BlueRock, notably Jude Samulski, PhD,, who was the scientific father of AAV-based gene therapy, working with Kathy High, MD, AskBio’s President of Therapeutics, who was the first female clinician to get a gene therapy approved [Luxturna®, marketed by Spark Therapeutics]. So that’s leadership.
What else is leadership? Leadership is, you invest in sustainable businesses. You make a commitment, you’re prepared to fail, but you’re in this for the long-term. Bayer is in cell and gene therapy and we’ve invested in this long-term.
We love platform companies, because it gives you an opportunity for learning loops. When you believe in something and it’s meaningful innovation, you need to be able to learn. And this is what platforms give you. Sometimes platforms can also converge, of course, and give you the next step in innovation, so I think that’s leadership.
GEN Edge: Bayer also recently announced a potentially $1 billion-plus collaboration with Mammoth Biosciences to use CRISPR systems to develop in vivo gene-editing therapies, starting with liver-targeted diseases.
Rommel: With the Mammoth genome editing collaboration, we’ve proven again that we invest for the long term. There’s no exclusivity on their technology.
GEN Edge: What about exclusivity in the liver disease indication?
Rommel: Indication, yes, but not for an organ. There are many different diseases, but we are not having exclusivity of liver [diseases]. Let’s be specific: Sometimes we target the liver by gene therapy or genome editing. But the disease that originates from the liver is a systemic disease that manifests itself in different tissues and organs.
There are specific pathologies that are in the liver and limited to the liver, and there are pathologies or diseases that by patho-physiological changes are triggered by and derived from the liver but causing other tissue and cell and organ diseases. I can’t reveal the indications.
The technology is not exclusive, and liver is not exclusive. However, we have secured a few indications that are either liver or linked to the liver. But we’re not overnight becoming a liver company. We see other opportunities.
We see the Mammoth technology in two ways. One is an enabling technology that you can apply to cell therapy—for instance, working with our colleagues at BlueRock—or it can be a stand-alone, therapeutic approach, of course, by gene correction in its own right.
GEN Edge: So that’s how it would fit in with Bayer’s cell and gene therapy then?
Rommel: Absolutely. We will continue to go down this road. Gene therapy can be a replacement augmentation. Genome editing allows you in situ gene corrections and gene regulation, which a vector system like AAV gene therapy heretofore could not provide, but you can combine them very well. And having the experience with AAV and tissue targeting is a springboard into Mammoth’s technology, again enabling for cell therapy.
GEN Edge: Does Bayer see both approaches as being able to coexist within that cell and gene therapy umbrella?
Rommel: Yes, absolutely. It’s not only that they can. They have to, in order for us to create the value first and foremost for the patient and for the business. They have to coexist.