BioNTech SE

Something changed for Bill Anderson when he turned 50. He was ascending the ranks of Roche’s Genentech, but the Texas native felt like he was stuck in the same loop year after year. The company would conduct employee surveys that would bring back tepid results, spurring management to vow to improve work processes. It would roll out initiatives with names like “Bureaucracy Buster,” Anderson said, and then the cycle would repeat the following year. Anderson compared the experience to “Groundhog Day,” the 1993 comedy in which Bill Murray’s character relives the same day, over and over. “After 20 years of that, I turned 50 and I literally said, ‘I’m not going to keep doing this,’” Anderson said. “There’s either got to be a better way, or I’m going to do something else. I’ll go do a startup. I’ll go teach. I’m not going to just turn the corporate crank anymore.” Now 58, Anderson finds himself in a different world today. He left Roche in 2023 to take one of the most difficult jobs in the corporate world — leading Bayer, the German conglomerate with mountains of debt and massive lawsuits stemming from its 2018 acquisition of Monsanto. The pharma business relied on aging blockbusters like Xarelto and Eylea, and its pipeline was thin. The stock price was grim, falling over 80% over the past decade and down 59% since Anderson started. Fellow countrymates BioNTech and Merck KGaA are both now more valuable than Bayer, a storied German brand. The silver lining of all that tumult is the chance to try something new. Long frustrated by bureaucracy, Anderson now gets the chance to break the cycle and develop a new way of running a large drugmaker. While there are signs of promise, a long road lies ahead for Bayer’s turnaround. Anderson’s two-year anniversary as CEO is in June. And next week, when Bayer shares its fourth-quarter earnings results, it will provide the latest look into how Anderson’s plan is going and if investors buy that he can save Bayer. On the tail end of a 17-stop, monthslong road trip, Anderson sat down with Endpoints News this month in midtown Manhattan. Sipping a mint tea in a black blazer over a patterned T-shirt, he speaks with the slightest hint of southern twang from growing up in Lake Jackson, TX, offset by decades of globetrotting. He is a straight shooter in assessing Bayer. A year ago, he likened the company to his own gruesome leg injury. He fell off a skateboard one Sunday morning in June 2021, shattering his right femur in four places. That was basically Bayer, he told investors and Wall Street analysts in March 2024. “We’re a high-impact, mission-driven company with three great businesses,” Anderson said, referring to its pharma, consumer health, and agriculture units. “But we’re also badly broken in four places.” Bayer’s “four breaks” were lapsing patents on key drugs without a sufficient pipeline, high debt, litigation fallout, and a bureaucracy preventing people from doing their best work, Anderson said. For his broken femur, Anderson spent 11 nights recovering in the hospital and a year in physical therapy. A year after making those comments, Anderson said Bayer has made “good progress,” though it’s still in the earlier stages of the turnaround. The pipeline is being replenished, fueled by five positive Phase 3 readouts in 2024 for key drugs like the chronic kidney disease therapy Kerendia , the prostate cancer treatment Nubeqa , and an experimental compound for menopause called elinzanetant . There were no negative Phase 3 readouts in 2024, Anderson added. The debt is being paid down, and Anderson is dedicating much of his time to trying to contain the legal liabilities. Bayer has already paid over $10 billion to settle tens of thousands of lawsuits claiming the Roundup weedkiller causes cancer, but tens of thousands of suits are still pending. “If we don’t fix that, we don’t have a future,” Anderson said. Since Anderson’s Groundhog Day moment eight years ago, he has formed his own philosophy for running a large company. It’s called Dynamic Shared Ownership. That sounds a lot like corporate jargon, but Anderson insists it’s fundamentally different. In a nutshell, DSO eliminates layers of management and leaves smaller teams with more decision-making power. These teams set their own measurable goals for 90-day cycles and can borrow talent from other teams. He found inspiration outside the drug industry. One of his favorite examples is Buurtzorg Nederland, a Dutch home-care organization founded by nurses in 2006. Buurtzorg now has over 16,000 employees with an administrative office of less than 100 workers and only two directors. It relies on small, self-managed teams of nurses to make most decisions. “I don’t really believe in the concept of the professional manager,” Anderson said. “We got to get the whole organization into a lean, mean fighting machine instead of an old corporate bureaucracy.” The DSO rollout is nowhere near as dramatic an idea as Buurtzorg, but it is reshaping Bayer. The US pharma unit, for instance, has reduced the number of managers by 40% under the new system, according to the company. Bayer has reduced its workforce by about 5,500 full-time employees in the first nine months of 2024. And, symbolically, Anderson replaced a 1,362-page rule book with a 14-page code of conduct. The moves are not without challenge, heightened by Anderson’s status of coming into Bayer as its first American CEO and pushing for radical change. German labor laws of codetermination, which give a legal right to employees to participate in company decisions, mean he must align with powerful works councils that represent employees. Brent Massmann left his role as a key expert within Bayer’s crop sciences unit last month, taking to LinkedIn to share his own DSO observations. Some managers have been “greatly impeded by dilution and dispersion of decision authority and by proliferation of non-value work,” he wrote. He also saw “valueless efforts to package work into” 90-day work cycles. It remains to be seen if this is moving the needle for investors. Berenberg analyst Sebastian Bray described two things that he thinks could spur a stock rally: reversing years of declining earnings per share, or landing decisive legal wins. “Neither occurrence seems imminent,” he wrote to investors in November, a statement that has held true since then. The balance sheet offers a sobering assessment of Bayer’s future. The company remains in the penalty box for investors with its debt, lawsuits and low earnings. Net sales fell by about 6% in 2023 from the previous year, and Wall Street forecasts another year-over-year decline to end 2024. Xarelto, Bayer’s best-selling medicine, is seeing accelerating declines in year-over-year sales, even before key patents expire in 2026. Anderson is transparent about these challenges, and he acknowledges that even DSO on its own cannot fix Bayer. “I wish it was that simple,” he said. Bayer’s pharma future needs to find replacements for Eylea and Xarelto. Anderson’s philosophy is simple: Great drugs lead the way, not existing franchises. He has seen that play out at Biogen with multiple sclerosis drugs, and at Roche and Genentech with Hemlibra in hemophilia or Ocrevus and Evrysdi in neuroscience. “A great molecule trumps everything,” he said. “The molecule makes the franchise, not the other way around.” Nubeqa may be that molecule. First approved in the US in 2019, the prostate cancer drug has surpassed €1 billion in sales through the first nine months of 2024, up 77% from the same period a year ago. It is the most important growth driver of Bayer’s pharma business. That success, Anderson said, can be attributed to DSO. Nicole Dinello, a pharma commercial veteran with over 30 years in the industry, arrived at Bayer just before Anderson did. She helped launch Nubeqa and shared numerous examples of how DSO changed how she and her team work. On their own, the changes aren’t earth-shattering. They removed two layers of management above her. Her team started making faster decisions. When someone asked what the team is doing for Spanish speakers in the US, they decided in the same meeting to translate a TV ad into Spanish and create a website and patient materials in Spanish. In a different instance, Dinello brought in a marketer from the cardiovascular business who helped craft Nubeqa’s social media strategy, working a few hours a week on that project. Each example adds into a better-functioning business. “It would never have occurred to me to go to the cardiovascular team and poach their talent,” Dinello said. “DSO feels different.” Anderson is no longer living through another Groundhog Day. But will his best efforts and new work philosophy be enough to save Bayer?

In April 2023, at the American Association for Cancer Research (AACR) annual meeting, Moderna and Merck announced detailed information about the phase 2b clinical trial of mRNA-4157 in combination with Keytruda for the treatment of melanoma. The study demonstrated that in patients with advanced melanoma, approximately 79% of patients who received Moderna's mRNA-based cancer vaccine in combination with Merck's immune checkpoint inhibitor Keytruda remained recurrence-free after 18 months, compared to 62% of patients who received Keytruda alone. Both companies stated their plans to initiate phase 3 clinical trials by the end of this year. Following the success of mRNA vaccines against COVID-19, tumor treatment is poised to become the next significant field for mRNA vaccines. We have entered a new era in cancer therapy, although there is still some way to go before widespread product application. mRNA vaccines involve delivering mRNA encoding antigen proteins into the human body, which is then translated directly into antigens, inducing an immune response. Unlike DNA and viral vector-based vaccines, mRNA vaccines are non-integrating and non-infectious, eliminating the potential risk of infection or insertional mutations and offering a higher level of safety. Additionally, mRNA has transient expression in the body, allowing for repeated administration. The outbreak of the COVID-19 pandemic has facilitated the successful application of mRNA vaccines, but beyond infectious diseases, these products have tremendous potential in the field of tumor treatment. Distribution of mRNA vaccine indications (partial)According to Boston Consulting Group's forecast, the entire mRNA vaccine market is projected to reach $23 billion by 2035. Within this market, mRNA cancer vaccines are expected to account for a 32% share, approximately $7.36 billion. This field of research is rapidly advancing at an unprecedented pace and showing promising prospects. Compared to many infectious disease vaccines, only a few cancer vaccines have been approved for human use. Cancer vaccines refer to those that can stimulate the body to generate active, specific immune responses against cells or molecules favorable for tumor growth, either within tumor cells or the tumor microenvironment (TME). Cancer vaccines can be classified into preventive and therapeutic categories. Currently, well-known vaccines such as HPV and HIV belong to the preventive category, while therapeutic cancer vaccines have yet to be commercialized on a global scale. In the form of mRNA vaccines, specific tumor antigen proteins can be synthesized within the human body, thereby inducing a targeted immune response against tumors. Unlike existing PD-1 inhibitors and CAR-T cell therapies, mRNA cancer vaccines can mobilize the entire immune system of patients, triggering a more potent and specific immune response. Tumor antigens can be categorized into two types: tumor-associated antigens (TAA) and tumor-specific antigens (TSA). TAAs are expressed in both normal tissues and tumors, but they are typically overexpressed in tumors. As a result, TAAs have weaker tumor specificity and immunogenicity and are susceptible to central immune tolerance. This has been one of the main challenges in developing cancer vaccines. TSAs, also known as neoantigens, differ from TAAs in that they are typically not expressed in normal cells, possess stronger tumor specificity and immunogenicity, and can bypass central T-cell tolerance to self-epitopes. TSAs are observed in most tumors. A study analyzing HLA-bound peptides across 13 different tumors (a total of 2,488 samples) revealed that each tumor may generate dozens to thousands of different neoantigens. However, it is important to note that TSAs exhibit high heterogeneity, with the types and quantities of mutations varying even within the same patient. This poses challenges in the screening and identification of TSAs, which are considered optimal targets for anti-tumor therapies. While mRNA synthesis is fast and cost-effective (GMP-grade mRNA can be produced within three weeks), the prediction phase for neoantigens may require more time and resources. Furthermore, during the vaccine preparation process, patients' conditions may change, potentially leading to missed optimal treatment windows. However, fortunate enough, the accuracy of neoantigen prediction and identification has been improved through the application of current large-scale high-throughput sequencing methods and artificial intelligence. The emphasis on these two different types of antigens roughly represents the two directions in current development of universal and personalized tumor vaccines. However, this categorization is not absolute. Upon reviewing the pipelines of vaccine giants like BioNTech and Moderna, it is evident that both companies have ventured into these areas. During the development of tumors, central immune tolerance and peripheral immune tolerance to tumor-associated antigens (TAAs), such as immune checkpoint pathways and the tumor microenvironment, pose two major challenges that limit the effectiveness and duration of cancer vaccines. To address central immune tolerance, combinations of multiple TAAs or multiple tumor-specific antigens (TSAs) can be used. To overcome peripheral immune tolerance, the concurrent administration of immune checkpoint inhibitors (such as anti-PD-(L)1 and anti-CTLA-4) and other drugs can be employed. Furthermore, regarding the antigen prediction challenge faced by personalized mRNA cancer vaccines, as individual data accumulates, it is gradually becoming possible to establish shared neoantigen libraries to address antigen prediction issues for the same or different types of cancer. Although this is a lengthy process, it is achievable. Over time, this will significantly accelerate the production process. Currently, there is a consensus in the industry regarding the application prospects of mRNA cancer vaccines, which are primarily focused on inoperable tumors and the prevention of recurrence after surgery, radiation therapy, or chemotherapy. Researchers are integrating multiple approaches to advance mRNA cancer vaccines at the forefront of immunotherapy to achieve better therapeutic outcomes. For example, the combination of Moderna's mRNA cancer vaccine mRNA-4157 and Merck's PD-1 therapy Keytruda has shown promising results in Phase II clinical trials, marking a breakthrough in the clinical validation of mRNA cancer vaccine concepts. However, it is important to acknowledge that there is still a considerable journey ahead before the actual products can be implemented. The content above comes from the network. if any infringement, please contact us to modify.

Keymed Biosciences is a prime example of a young Chinese biotech churning out pipeline candidates ripe for out-licensing to Western drugmakers. The Chengdu-based company, which already markets its own drug in China, has forged four NewCo deals since July. In the NewCo model, a biotech in China out-licenses a drug candidate to a startup formed by Western investors for clinical development in the US and/or Europe. Keymed is now one of the most active deal-slinging Chinese biotechs at a time when drug development in China has stepped into the global spotlight. For drugmakers looking to build up their pipelines, the country’s molecules are of interest, given that they can be cheaper to license than programs developed by US biotechs and are more quickly produced in China, with its high-grade chemistry oversight, than the rest of the world. Keymed made three deals in January ( Ouro , Prolium and Timberlyne ) and one in July ( Belenos Biosciences ). It also announced a licensing deal for antibody-drug conjugates with AstraZeneca in early 2023. “From our perspective, we do like more China assets to be seen and to be developed out of China,” Keymed’s head of business development Ivy Geng said in an interview. She hopes experimental drugs from Chinese biotechs will remain in the spotlight, and she wants assets from the country’s rapidly expanding biotech industry to be developed in other countries for patients around the globe. Keymed may only be a nine-year-old biotech, but it’s quickly made a name for itself among US biotech investors. The drug developer was founded by PD-1 antibody leaders. CEO Bo Chen helped invent and develop toripalimab, the first PD-1 antibody developed and approved in China. And Changyu Wang, Keymed’s SVP for drug discovery and development, helped lead development of Bristol Myers Squibb’s PD-1 Opdivo, which opened up the immunotherapy field a decade ago. With these experts at the helm, Keymed drummed up investor support and went public on the Hong Kong Stock Exchange in 2021, in an approximately $400 million IPO. Two years later, it forged the licensing deal with AstraZeneca for a Claudin 18.2 ADC for $63 million upfront and up to $1.1 billion in milestones. Keymed is sharing those payments with its partner Lepu Biopharma. In early 2022, Geng joined Keymed to kick-start its business development beyond China. The company had a bustling pipeline of investigational treatments, but little clinical expertise based in the US or the resources to pursue development outside of China. It then turned to Western investors like OrbiMed and Bain Capital, which have both built up their China networks over the years and have done multiple deals bringing Chinese assets to the US. Keymed is active in its NewCo partnerships, holding board seats and snagging decision and information rights so it remains in tune with the future development of its drugs. And rather than focusing on the size of the upfront payments, Keymed prefers to play the long game and get between a 20% and 30% equity stake in each new company, finance chief Ryan Zhang said. Keymed also believes the talent at the NewCo is of utmost importance, Geng said. It now has about 1,300 employees. Having direct access to its partners will also allow Keymed to learn the nuances of the US clinical trial landscape, though Zhang noted that the company has no immediate plans to build a physical footprint in the US. Geng declined to disclose Keymed’s business development plans. But it’s clear that the NewCo model is flourishing. Other China-based drug developers have done similar deals, including Hengrui with Aiolos and Kailera, DualityBio with Avenzo Therapeutics, and WuXi Biologics with Candid Therapeutics. In addition, BioNTech, Merck, GSK, AstraZeneca and others have acquired assets or companies in China in recent years. The rush to secure China-developed drugs can be summed up by the scene at the Shanghai airport, according to one biotech executive, who noted how common it is now to see pharma-branded backpacks there.