Bayer is counting on its growing oncology business to deliver one third of the $30 billion in pharmaceuticals sales it has committed to generating by 2030.
That would translate to $10 billion in sales by 2030 from Bayer’s oncology business, a goal the pharma giant set last year, reaffirmed by its top oncology executives in an exclusive interview with GEN Edge. Bayer says $10-billion sales would catapult it into a top-10 seller of cancer drugs, up from its current perch at No. 14.
“The way to get there is, one, to really focus on the four large tumor types, and build either a big blockbuster in one of these [areas] or have a depth of assets in a given tumor type—making sure that we have a play where there’s a large market,” said Christine Roth, Executive Vice President and Head of Bayer’s Oncology Strategic Business Unit.
The second area of focus Bayer is pursuing, she continued, is fill-and-flow—attracting and advancing drug candidates showing “highly novel, highly compelling science that’s focused against targets or patient populations of high unmet medical need.”
“The days of following the science wherever it takes you, letting the research department’s intellectual curiosity drive where you go in the future, and launching a broad number of new medicines but none of them really becoming substantial medicines—$1 billion in sales, for example—those days are over, because the challenges in commercialization are just getting bigger and bigger,” Roth added.
“The days of following the science wherever it takes you, letting the research department’s intellectual curiosity drive where you go in the future, and launching a broad number of new medicines but none of them really becoming substantial medicines—$1 billion in sales, for example—those days are over.”
Roth discussed the promise and challenges of growing Bayer’s oncology business with Tara Frenkl, MD, MPH, Senior Vice President and Head of Oncology Development, with GEN Edge during the recent J.P. Morgan 41st Healthcare Conference.
They acknowledged several challenges to Bayer delivering on cracking the top-10 group of cancer drug developers, a list Roth said included Bristol-Myers Squibb (BMS), Roche, and AstraZeneca. That list is also likely to include Merck & Co. given the $20.937 billion generated in 2022 by its blockbuster immuno-oncology drug Keytruda.
Bayer’s first challenge is the post-COVID-19 treatment landscape, in which patients have foregone routine screenings and cancer care worldwide—the conclusion of a review of 33 peer-reviewed studies published last September.
“One of the benefits that we have is that several of our medicines are oral. During the pandemic, where many vulnerable cancer patients were hesitant to come into institutions to receive IV based therapies, giving a physician an option for an oral-based therapy was a big boon,” Roth said. Other oncology drug developers with oral treatments enjoyed the same advantage.
The cost of COVID treatments, Roth said, has compelled numerous countries to contain costs for cancer drugs in varying ways, from curbing prices to limiting the number of patients eligible for a certain class of therapy in a given year: “That’s, unfortunately, going to limit patients’ access to innovation in many ways.”
But Bayer can still grow in oncology, she added, by making use of growing FDA willingness to accept earlier endpoints like metastasis-free survival and surrogate endpoints such as residual disease—as well as stepping up efforts to develop emerging classes of treatments.
Bayer says growing its oncology business will rest in part on its ability to develop new drugs in three modalities or “pillars”—precision molecular oncology (PMO), immuno-oncology, and targeted radiation therapies (TRTs).
“If there’s an unmet need in lung cancer, the beauty of having these three platforms is, if you find a novel target, we can work across those platforms to say, is this a target that lends itself to I/O, to PMO, or to potential TRT or some other modality, because we’ll have depth of expertise there,” Roth said.
That depth, she explained, comes from Bayer’s access to external innovation through business development, collaborations with smaller companies, academic partnerships, and acquisitions.
“We’ve had the most success in terms of BD [business development] in the early stage. We continue to look for something that’s a little bit later or mid-stage. But those types of opportunities are few and far between, and there’s deep-deep competition and high-high costs associated with that,” Roth said. “Anything we would do in the mid- to late-stage has got to be something that’s a perfect intersection of the size of the opportunity, the fit with our strategy, and somewhere where Bayer is the ideal partner. And that would give us a better opportunity to secure that type of external innovation.”
Bayer has acquired several companies in recent years, but chosen to let them largely chart their own R&D paths as “arm’s length” subsidiaries—including gene therapy developer Asklepios BioPharmaceutical or AskBio (acquired for up to $4 billion in 2020); cell therapy developer BlueRock Therapeutics (up to $600 million in 2019), and Vividion Therapeutics (up to $2 billion in 2021), which applies its chemoproteomics platform to develop precision drugs for cancers and immune disorders.
Two programs that originated at Vividion are expected to enter Bayer’s clinical cancer pipeline this year. One is BAY 3605349, designed to fight Nuclear factor erythroid 2-related factor 2 (NRF2) mutant cancers by targeting the KEAP1-NRF2 axis. The other is BAY 3630914, a signal transducer and activator of transcription 3 (STAT3) inhibitor. (Vividion also has preclinical programs targeting KEAP1-NRF2 in inflammatory bowel disease, and STAT3 in immunology.)
Vividion also raised its profile in cancer drug development in October, by agreeing to partner with precision oncology platform company Tavros Therapeutics to discover or target four oncology targets across an initial five-years. Vividion agreed to pay Tavros $17.5 million upfront and up to $448 million in payments tied to achieving milestones. Vividion also holds options for up to five more targets, in return for paying Tavros an additional up to $482 million.
Bayer boosted its ability to develop PMOs last year when it opened its $140-million Bayer Research and Innovation Center (BRIC) in Kendall Square, Cambridge, MA.
Whatever modalities Bayer applies in developing drugs, three principles will guide the company’s efforts to bring new oncology drugs to market, Frenkl said.
“Patient centricity—the patient is at the center really of everything we do and how we develop our drugs. The quality, making sure that we’re asking the right questions with our trials, and setting a bar high enough that our medicines are really going to make a difference for patients. And then, ensuring that from the earliest stage of development, there’s a good value proposition that will carry through all the way to development, so that when we are ready to file and get approval, the drug will actually be reimbursable and therefore accessible to patients.”
Roth and Frenkl said Bayer won’t disclose its current oncology sales, or what proportion they make up of its total pharmaceuticals sales, which totaled €18.35 billion ($20.03 billion) in 2021, up 7.4% from 2020; and €14.39 billion ($15.72 billion) in Q1-Q3 2022, up 7.5% from a year ago. Bayer will report its full-year 2022 results on February 28.
Pharmaceuticals is Bayer’s second largest division, with only Crop Science generating higher sales and Consumer Health, lower.
However, the company has offered bits and pieces of its oncology sales in quarterly reports and public statements, much of it centered on its top-selling cancer drugs.
Bayer’s top selling cancer drug Stivarga® (regorafenib) racked up €458 million ($499 million) in the first nine months of 2022, up 28% from €357 million ($389 million) a year earlier, and €477 million (about $521 million) in 2021, up 0.4% from €475 million ($518 million) in 2020. Stivarga is a multi-kinase inhibitor indicated as standard-of-care third– or fourth-line treatment in metastatic colorectal cancer (CRC), as well as advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST), and hepatocellular carcinoma (HCC) in patients previously treated with another Bayer kinase inhibitor, Nexavar® (sorafenib).
Nexavar is Bayer’s next-highest seller in cancer, but trending down due to competition from lower-cost generic versions. The treatment saw its sales slide 36% in Q1-Q3 2022, to €221 million ($241 million) from €344 million ($375.5 million), on top of a 32% year-over-year decline in 2021, when sales fell to €435 million (about $475 million) from €639 million ($697.5 million) in 2020. In addition to unresectable HCC, Nexavar is indicated for advanced renal cell carcinoma and locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) refractory to radioactive iodine treatment.
Bayer’s fastest-growing marketed cancer drug is Nubeqa® (darolutamide), an oral androgen receptor inhibitor jointly developed with Finland-based Orion Pharma. Nubeqa first won FDA approval in 2019 to treat forms of non-metastatic castration-resistant prostate cancer (nmCRPC). In August 2022, the FDA also approved Nubeqa for metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel.
Nubeqa has seen its sales soar in Q1-Q3 2022 to €308 million (about $336 million) in Q1-Q3 2022, up 105% from €150 million (about $164 million) a year earlier. Nubeqa generated €219 million ($239 million) in 2021 (Bayer has not disclosed the 2020 figure).
“Nubeqa doubled sales between 2021 and 2022, and our ambition is to double sales again from 2022 to 2023,” Roth said.
Nubeqa is steadily if slowly advancing toward Bayer’s peak-year sales forecast of $3 billion in 2030. Bayer tripled that forecast last year from $1 billion after the company released positive results from the Phase III ARASENS trial (NCT02799602) showing that the combination of Nubeqa, androgen deprivation therapy (ADT), and docetaxel significantly increased overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) compared to ADT and docetaxel alone.
Roth said Nubeqa was an example of Bayer building pipeline depth and expertise in prostate cancer, one of the four most common cancer types in the U.S. and globally based on numbers of new cases. The others are breast, lung, and colorectal cancer.
“We’re looking to do the same in an additional major tumor type through our pipeline and life cycle management efforts,” Roth said. “Whether that’s lung cancer, whether that’s deeper into colorectal cancer, only our pipeline will tell us.”
Another Bayer cancer treatment, Xofigo™ (radium Ra 223 dichloride), generated €261 million (nearly $285 million) in 2021, down slightly from €262 million ($286 million) in 2020. The company has not disclosed 2022 sales for the radioactive agent, which is indicated for patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.
Bayer has not disclosed any sales figures for two other marketed cancer drugs in its portfolio. One is Aliqopa® (copanlisib), a pan–class I Phosphatidylinositol 3-kinase (PI3K) inhibitor indicated for third-line relapsed follicular lymphoma in adults.
The other is Vitrakvi® (larotrectinib), the first tropomyosin receptor kinase (TRK) inhibitor approved by the FDA in 2018. Vitrakvi was co-developed by Bayer with Loxo Oncology, acquired in 2019 by Eli Lilly for $8 billion and since renamed Loxo@Lilly. Bayer has not disclosed sales figures for Vitrakvi, though Roth said its sales grew over 40% last year.
Vitrakvi is unusual in that it’s not approved for a specific tumor type—but for patients of all ages with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation. The drug is also indicated for patients with solid tumors that are metastatic or where surgical resection is likely to result in severe morbidity, have no satisfactory alternative treatments, or that have progressed following treatment.
To reach its 2030 goal, Bayer needs to maximize the value of its marketed drugs by adding new indications.
Over the next 18 months, Frenkl said, Bayer will study if Nubeqa’s mHSPC population can be expanded to patients who forego docetaxel, “because a lot of patients opt not to have that chemotherapy.” Bayer is also assessing Nubeqa plus a luteinizing hormone releasing hormone analogue in locally advanced prostate cancer at very high risk of recurrence, through the Phase III DASL-HiCaP trial (NCT04136353), which Bayer is conducting with the Australian and New Zealand Urogenital and Prostate Cancer Trials Group.
Also in a Phase III trial (NCT02367040) is Aliqopa, which is under study in combination with Roche (Genentech)/Biogen co-marketed Rituxan® (rituximab) in relapsed indolent B-cell non-Hodgkin’s lymphoma. Stivarga is in a Phase II trial in combination with BMS’ Opdivo® (nivolumab) in recurrent or metastatic solid tumors (NCT04704154).
In addition, Leverkusen, Germany-based Bayer is in Phase I trials for two advanced solid tumor candidates developed through a collaboration with the German Cancer Research Center (DKFZ). BAY 2416964 is a Phase I aryl hydrocarbon receptor (AhR) inhibitor under study as monotherapy (NCT04069026) and with Keytruda (NCT04999202) in advanced solid tumors. BAY 2965501 is a diacylglycerol kinase zeta inhibitor in an open-label, first-in-human, dose escalation and expansion study launched last November (NCT05614102).
The Bayer-DKFZ collaboration has also yielded a preclinical candidate—BAY 2862789, a DGK-alpha inhibitor indicated generally for cancer. Also in preclinical phases are a pair of advanced prostate cancer candidates known as targeted Actinium conjugates—BAY 3546828, which originated with Lantheus Holdings, and BAY 3563254, which originated with Noria Therapeutics and its subsidiary PSMA Therapeutics, both of which Bayer acquired in 2021 for an undisclosed price.
The rest of Bayer’s cancer pipeline includes six Phase I candidates:
- Bapotulimab (BAY 1905254), an ILDR2 (immunoglobulin-like domain containing receptor 2) function-blocking antibody being co-developed with Compugen and under study as monotherapy and in combination with Keytruda in advanced solid tumors and head and neck squamous cell carcinoma (NCT03666273).
- Elimusertib (BAY 1895344), an ataxia telangiectasia and Rad3-related (ATR) kinase inhibitor under study for advanced solid tumors, non-Hodgkin’s lymphoma, and Mantle cell lymphoma (NCT03188965); advanced solid tumors (NCT04095273); and advanced solid tumors excluding prostate cancer and ovarian cancer (NCT04267939).
- BAY 2666605, a Schlafen 12 (SLFN12)/Phosphodiesterase 3A (PDE3A) complex inducer being assessed in metastatic melanoma and advanced solid tumors expressing both SLFN12 and PDE3A proteins (NCT04809805).
- BAY 2701439, an antibody-based Human epidermal growth factor receptor 2-targeting thorium conjugate (HER2-TTC) being investigated in HER2-expressing breast and gastric/gastroesophageal cancer, and other HER2-expressing advanced cancers. (NCT04147819).
- BAY 2927088, a selective mutant epidermal growth factor receptor (EGFR) inhibitor being studied with the Broad Institute of MIT and Harvard in advanced non-small cell lung cancer, EGFR mutation and HER2 mutation (NCT05099172).
- BAY 3375968, an anti-CC chemokine receptor 8 (CCR8) antibody under study as monotherapy and with Keytruda in advanced solid tumors (NCT05537740).
Roth celebrates her first year anniversary at Bayer on March 1, having arrived from GlaxoSmithKline (GSK), where she also served as Senior Vice President, Global Oncology Therapy Area Head. Six weeks later, she was joined at Bayer by Frenkl, who worked with Roth at GSK as Senior Vice President, Head of Medicine Development Leaders in Oncology.
“One of the reasons why we were attracted to new opportunities and specifically Bayer was the real opportunity to help build upon the strong foundation that has been laid in oncology, but really accelerate growth into building this into a business at scale, a business that’s fit for future growth, and one that achieves a top-10 status in the 2030 timeframe,” Roth said.