Skin disorder therapeutics(Dermira)

Pictured: Illustration of stacks of coins and a graph charting growth / iStock, Intpro In March 2023, Sanofi acquired the diabetes drug Tzield, along with its owner Provention Bio, for $2.9 billion. While not among the largest deals in the biopharma industry, it’s still a sizeable sum of money—especially for a treatment once discarded by another pharma giant. Initially developed by MacroGenics, the intravenous antibody treatment was scooped up by Eli Lilly in 2007, but Lilly dropped it three years later after a clinical trial in recently diagnosed type 1 diabetes patients failed to show a significant reduction in daily insulin dose or blood sugar levels in the treatment group compared to placebo. But it wasn’t the end of the road for Tzield. In 2018, MacroGenics licensed the drug to Provention for $6.1 million, according to SEC filings. In 2022, Sanofi took an interest, partnering with Provention to commercialize the drug. Late last year, the investment paid off—the FDA approved Tzield, and Sanofi moved forward with a complete acquisition of Provention and its drug. Such a convoluted history for therapeutics is not uncommon. Pharmaceutical companies may decide to sell the rights to their drug development programs when they have no intention of manufacturing the drug, or the research process doesn’t turn out as planned. However, sometimes the offloaded products perform better elsewhere, leading to big buyouts as companies try to expand their portfolios. The decision to license or sell a drug depends on profitability and a company’s strategic mission, said Andrew Lo, director of the Laboratory of Financial Engineering at MIT Sloan School of Management. “Even if a particular drug program is likely to be successful, and even if it generates a couple hundred million dollars a year in revenue, that might not be enough to justify putting the resources of the company to that drug because the same resources can be developing a billion dollar a year drug,” Lo told BioSpace. Similarly, if a company halves its work in a specific area, it may drop all products even if they’re successful. These decisions also depend on whether a company “believes” in the science of a drug, Lo said. Even if a drug doesn’t do well in clinical trials, another company may predict it will do well in the future and decide to buy it. In those cases, the original owner often retains an ownership stake in the product if it does well—to avoid the “egg on your face” of giving up a good product, as Lo described. As for acquisitions, those decisions depend on whether the acquiring company values all of the target company’s assets or just some. Lo said the trend of drugs changing hands would continue as some companies fall into financial need and sell their assets. “Stay tuned because the next six to 12 months are going to be periods of very active licensing deals and acquisitions." Here are a few more examples of drugs that ended up under the purview of large pharmaceutical companies after being dropped. 1. Momelotinib: Gilead’s Loss, GSK’s Gain First sale: YM Biosciences to Gilead Sciences for $510M (2012) Second sale: Gilead Sciences to Sierra Oncology for $3M (2018) Third sale: Sierra to GSK for $1.9B (2022) Momelotinib is a medication for patients with myelofibrosis, a form of bone marrow cancer. Gilead acquired the drug for $510 million in its 2012 acquisition of YM Biosciences, which had merged with Cytopia Limited in 2009. Gilead sold it to Sierra Oncology in 2018 for $3 million after clinical trials showed mixed results. Under the new ownership, the drug succeeded in clinical trials, and in June 2022, it was submitted to the FDA for approval. By then, GSK had already agreed to acquire the company for nearly $2 billion. Sierra awaits the agency’s decision, expected in June 2023. 2. Lebrikizumab: Roche’s Loss, Lilly’s Gain First sale: Roche to Dermira for $80M (2017) Second sale: Dermira to Eli Lilly for $1.1B (2020) Lebrikizumab is a monoclonal antibody used to treat atopic dermatitis. Dermira paid $80 million upfront to acquire the drug from Roche Group in 2017, and two years later, the FDA granted lebrikizumab fast-track designation. In 2020, Eli Lilly acquired Dermira for $1.1 billion. Lilly submitted the drug for approval in November 2022. 3. Zejula: Merck’s Loss, GSK’s Gain First sale: Merck to Tesaro for $7M (2012) Second sale: Tesaro to GSK for $5.1B (2019) Zejula (niraparib) is a poly ADP-ribose polymerase inhibitor that targets a family of proteins involved in cell response. Merck accepted $7 million upfront from Tesaro in 2012 to unload the drug from its portfolio. Five years later, the drug was approved for ovarian, fallopian tube or primary peritoneal cancer patients. Zejula’s success led GSK to acquire Tesaro for $5.1 billion in 2019. However, later concerns about PARP inhibitors led GSK to restrict the drug’s indications, even as the company explores Zejula’s utility for other cancer types. 4. Veltassa: Amgen’s Loss, Galenica’s Gain First sale: Amgen to Relypsa for $8.2M upfront (2009) Second sale: Relypsa to Galenica for $1.5B (2016) Veltassa (patiromer) is a drug developed for treating hyperkalemia, or high potassium in the blood. Relypsa, an offshoot of Amgen, received the rights to Veltassa from the parent company in 2009 for an upfront cost of $8.2 million. The drug was approved in 2015, and around the same time, Relypsa partnered with Vifor Fresenius Medical Care Renal Pharma—owned by Galenica—to commercialize the drug outside of the U.S. In 2016, Galenica fully acquired Relypsa for $1.5 billion and renamed the company CSL Vifor. 5. Cubicin: Lilly’s Loss, Merck’s Gain First sale: Eli Lilly to Cubist Pharmaceuticals for an undisclosed cost (1997) Second sale: Cubist to Merck for $8.4B (2014) In the late 1980s and early 1990s, Eli Lilly developed daptomycin, an intravenous antibiotic. However, the company suspended clinical trials after volunteers experienced adverse effects and discontinued its work on antibiotics altogether. Lilly then granted Cubist Pharmaceuticals the rights to develop and distribute daptomycin, which was approved in 2003 under the brand name Cubicin and 11 years later acquired by Merck for $8.4 billion. 6. Anidulafungin: Lilly’s Loss, Pfizer’s Gain First sale: Eli Lilly to Vicuron for $14M (1999) Second sale: Vicuron to Pfizer for $1.9B (2005) Vicuron obtained the antifungal drug anidulafungin from Eli Lilly in 1999 for $14 million. Initial Phase III clinical trials were successful, but in 2004 the FDA said a New Drug Application for the drug didn’t have enough data to support its efficacy, leading to lawsuits by shareholders per SEC filings. A year later, Pfizer acquired Vicuron for $1.9 billion. After submitting additional clinical data and adding another indication, the drug was approved in 2006 under the brand name Eraxis. Nadia Bey is a freelance reporter in North Carolina. She can be reached at beynadiaa@gmail.com.

Evommune team/courtesy of Evommune Evommune’s novel human tissue-based assay system is proving to be a key differentiator as the company develops therapies to control chronic inflammation in autoimmune diseases. “Working with human tissue puts us closer to the target and yields a model that is much more predictive of outcomes in the human immune system,” said Luis Peña, CEO of Evommune, in an interview with BioSpace. “Skin has all of the cell types that are needed to induce specific inflammatory pathways,” said Eugene Bauer, M.D., CMO of Evommune. The company’s human tissue model is an ex vivo system that uses living skin from human donors, allowing the model to reflect all the immune responses that occur across various tissues in the body that drive inflammation. Consequently, in this context, it is more robust, predictive and relevant than animal modeling. This most closely mimics a “real-time” look at immune pathways and how to find the best way to target and modify inflammation. The miniaturized technology enables hundreds of assays to be conducted to study both systemic and topical therapies. Evolving Immunology In seeking to evolve immune therapy, Evommune is looking at the following opportunities in treating patients: early intervention in their disease state, improving efficacy, increasing response rates in patients and enhancing safety. “Autoimmune diseases are, in fact, systemic inflammatory conditions that are often associated with serious co-morbidities including infections, cardiovascular events, renal disease and mental health issues, making early intervention and preventing disease progression extremely important,” Peña said. “The entire body is in an accelerated immune-response mode. So, we are trying to modulate the immune system to dial down some of these responses. “Existing therapeutics have improved our ability to treat inflammatory conditions, but in most diseases, they still only elicit a response in about half the patients treated and achieve a great response rate in only one-third of those,” he continued. “Creating medicines that have better efficacy and that induce remission is the goal for us.” Improving the safety pro drugs that treat autoimmune diseases could make a meaningful impact in this space. “We want to develop therapies that improve patients’ quality of life without putting them at risk for other factors,” Peña said. Evommune’s senior leadership and scientific teams are primed to do just that. Throughout their careers, they have helped bring more than 25 medicines to patients in need. As Peña noted, “the combination of scientific insights, drug development expertise and building companies makes this team a unique group.” Accomplished Team of Experts A testament to this is that Peña and Bauer were co-founders of Dermira, which Eli Lilly acquired for $1.1 billion to get the rights to lebrikizumab. The two had originally helped acquire this asset from Genentech, despite the drug having failed in prior Phase III trials for a different indication. “We saw that lebrikizumab had promise in atopic dermatitis. We believed lebrikizumab had been under-dosed in previous atopic dermatitis trials, mostly because of a focus on asthma,” Peña explained. “We adjusted the dose in a Phase II atopic dermatitis program and delivered strong data. Lilly bought us because of that drug and since then, lebrikizumab has had great data from their Phase III studies. We believe lebrikizumab will become a significant therapy for atopic dermatitis and the team at Evommune had the vision to make that happen,” he said. Before Dermira, Bauer was president and CMO of Peplin, Inc. (acquired by LEO Pharma) and shepherded Picato® through a global submission, which included the FDA and resulted in an approval for actinic keratosis. Additionally, the Evommune development team has been responsible for multiple new drug applications or biologics license applications, several investigational new drug applications and numerous other interactions with regulators, including four global clinical development programs. “That combination of intimate knowledge of both immunology and drug development is what separates Evommune from other companies in terms of our ability to move these novel therapies forward,” Peña said. Evommune is committed to this promise with the ongoing expansion of the team, including new management positions across R&D, CMC, legal, strategy and finance who also bring a wealth of diverse drug discovery and development expertise. A Multifaceted Pipeline Evommune currently has four programs in the pipeline. "The goal for all of our programs is to be best in class,” Peña said. “EVO101 for atopic dermatitis is an IRAK4 inhibitor, which is a very novel target.” A randomized, blinded, placebo-controlled Phase IIa clinical trial for patients with mild-to-moderate atopic dermatitis was initiated in Q3 2022. “We define ‘mild-to-moderate’ atopic dermatitis as affecting between 4 and 12% of an individual’s body surface area. For perspective, the palm of your hand is 1%,” Bauer elaborated. “Study participants will apply a 0.1% cream to the lesions twice daily for eight weeks.” Results will be scored using the eczema area severity index (EASI), which measures redness, scaling and thickness of lesions, as well as the extent and severity of the disease. In EVO101’s development work, Evommune’s human tissue model enabled researchers to recapitulate disease pathology and inflammatory mediators of atopic dermatitis. “Adding low-, mid- and high-potency topical steroids (current standard-of-care therapeutics) to the human tissue model provided a control set of efficacy data – a baseline by which we could then compare the performance of EVO101,” Bauer explained. EVO101, at the dosage being used for patients in the clinical trial, lowered inflammation levels to those comparable with doses of ultra-high potency steroids, but with high selectivity. “We believe this could become an alternative to standard-of-care therapies for atopic dermatitis,” Bauer said, that may be used to treat both adult and pediatric patients. “In addition, we now have a development stage program that could potentially be a ground-breaking oral therapy for mast cell-mediated diseases,” he said. “EVO756 is a completely novel compound that will target the treatment of mast cell-mediated diseases and inflammatory itch,” Peña said. EVO756 targets MRGPRX2, a receptor that exists on mast cells and peripheral neurons and regulates mast cell degranulation. EVO756 is targeted for the treatment of mast cell-mediated disorders with highly prevalent populations such as chronic spontaneous urticaria, interstitial cystitis and hereditary alpha-tryptasemia. In addition, preclinical data have shown that itch can be completely eliminated in mice: knocking out that receptor made it impossible to induce itch. “For patients with inflammatory diseases, itch can be severe and have a significant, negative impact on a patient’s quality of life. We think EVO756 could be a great oral therapy, that can act quickly to relieve itch,” Peña continued. Another program, EVO390, is in development for the treatment of mild-to-moderate psoriasis in the hope of slowing or halting disease progression. This therapeutic agent targets RORγt and has the potential to be best-in-class and the agent of choice for these patients. It may also serve as an adjunct therapy in more severe cases. “We believe it could be a broadly used therapy for psoriasis,” Peña added. “Our fourth program, currently in discovery, targets protein kinase C (PKC) theta,” Peña continued. The company has identified several potent molecules that may have broad anti-inflammatory activity, highly targeted to T-effector cell inhibition and T-regulatory cell activation. This may have utility across a number of inflammatory conditions such as rheumatoid arthritis, IBD, atopic dermatitis and psoriasis. In addition, because it is highly targeted, it has the potential to be safer than the JAK inhibitors and other systemic anti-inflammatory agents. “As a company, we understand the importance of working on multiple targets and managing a portfolio of compounds. This approach provides the opportunity to work on different agents, impact many diseases and make a difference in patients’ lives,” Peña said. The company’s discovery engine is working to identify new targets so the team can extend its therapeutic impact.