Eli Lilly Strengthens Obesity Pipeline with $1.925 Billion Acquisition of Versanis Bio

In the fiercely competitive weight-loss market, Eli Lilly and Company is accelerating its pace, leaving many pharmaceutical companies struggling to keep up.

At the end of April this year,GIP/GLP-1 Receptor Dual AgonistThe success of Tirzepatide's SURMOUNT-2 study propelled Eli Lilly's market value to soar, surpassing Johnson & Johnson to become the world's most valuable pharmaceutical company.The obesity sector has always been a key focus for Eli Lilly. In terms of performance, it is also Eli Lilly's flagship business, with a full-year revenue of $13.829 billion in 2022, accounting for 48.5% of total income.

On July 14, Eli Lilly and Company announced another forward-looking move in the weight-loss drug sector, declaring its acquisition of Versanis Bio, a company focused on cardiometabolic diseases and obesity.

According to the terms of the agreement, Versanis is eligible to receive up to $1.925 billion in cash, including upfront payments and subsequent milestone payments.

According to Dr. Ruth Gimeno, Vice President of Diabetes, Obesity, and Cardiometabolic Research at Eli Lilly and Company, Eli Lilly and Company acquired Versanis Bio.It values its deep understanding of activin biology."By combining Eli Lilly and Company's expertise in incretin biology with Versanis' deep understanding of activin biology, we aim to leverage the potential benefits of this combination for patients."

Moreover, Eli Lilly and Novo Nordisk have long been fierce competitors in the weight-loss field, and if this deal succeeds,It will provide Eli Lilly with a new mechanism for addressing obesity that Novo Nordisk does not have.This gives Eli Lilly a stronger advantage in this competitive landscape.

Versanis is not the only company that Eli Lilly has invested in within the weight loss field. Through multiple acquisitions, Eli Lilly's layout in the obesity sector has become increasingly clear.

Versanis's core pipeline, Bimagrumab, was initially developed by Novartis for the treatment of pathological muscle loss and weakness but was abandoned after clinical failures. Versanis obtained the authorization for the drug through financing and successfully redirected it into the weight-loss track.

Bimagrumab is a monoclonal antibody that binds to activin type II A and B receptors to block activin and myostatin signaling. Combining incretins with bimagrumab has the potential to further reduce fat mass while preserving muscle mass and may lead to better outcomes for patients with obesity and obesity-related complications.

Previously, the results of the Phase II clinical trial of Bimagrumab showed that patients who received treatment for 48 weeks showed significant improvement in multiple indicators compared to the placebo group.Bimagrumab is currently in Phase IIb clinical trials to evaluate its efficacy as a monotherapy or in combination with semaglutide for the treatment of overweight or obesity in adults.

Another potential advantage of Bimagrumab is that it may be able toMaintain Weight Loss Results for a Longer PeriodEarly trial data shows that people can maintain weight loss for 12 weeks even after stopping treatment. In contrast, patients often regain weight quickly after discontinuing GLP-1 drugs. Previously, Versanis President Lloyd Klickstein stated in an interview: "Generally, when people lose weight, their metabolism slows down. However, since bimagrumab helps preserve muscle mass, and muscle burns more energy than fat, this treatment can help individuals maintain a faster metabolism and strengthen resistance to weight rebound."

For Eli Lilly, although the company has shown outstanding market performance in the obesity field, most of the drugs it currently holds are GLP-1 drugs, which may cause patients to lose both fat and muscle simultaneously. If the patients receiving treatment are elderly, the use of these drugs might even make them more frail.bImagrumab can reduce fat without losing muscle., in terms of patient medication safety, it is superior to other drugs.

This acquisition also reveals Eli Lilly's ambition to continuously consolidate and even expand its strength and position in the metabolic field. It can be said that Eli Lilly has been making frequent moves recently in terms of acquisitions and product introductions.

▲ Eli Lilly's Cooperation and Acquisitions in the Weight Loss Field

Versanis is not the only company that Eli Lilly and Company has invested in within the weight loss field.Eli Lilly and Company completed four acquisition deals in just the first half of 2023, including Versanis, Emergence, DICE, and Sigilon.Sigilon is a biopharmaceutical company aimed at developing functional therapies for patients with various acute and chronic diseases. Sigilon's candidate products are based on non-viral engineered cell therapies, designed to produce a wide range of functional or therapeutic molecules that may be missing or insufficient in patients with conditions such as diabetes. Sigilon’s technology platform, the Shielded Living Therapeutics™ platform, encapsulates engineered human cells within its proprietary Afibromer™ biomaterial matrix to protect the cells from immune rejection. Leveraging this technology platform, Sigilon’s cell encapsulation technology has the potential to develop long-lasting, repeat-dose "off-the-shelf" functional curative therapies that do not require modification of the patient’s genes.

Eli Lilly and Company partnered with Sigilon as early as 2018 to co-develop encapsulated cell therapies, including SIG-002, for the treatment of type 1 diabetes. The goal was to enable patients to摆脱持续的疾病管理 by sensing blood glucose levels, restoring insulin secretion, and providing long-term release. This acquisition allows Eli Lilly to gain access to the core pipeline SIG-002, a product designed to replace the islet cells responsible for the root cause of diabetes and reduce the need for patients to rely on insulin to control blood glucose levels.

"Despite significant advances in the treatment of people with type 1 diabetes, many patients continue to live with a high burden of illness," said Dr. Ruth Gimeno. "By combining Sigilon's talent and expertise in cell therapy with the knowledge and skills of Eli Lilly and Company's R&D team,We will increase the opportunities to create innovative islet cell therapy solutions., to improve care for patients with diabetes."

Although SIG-002 is currently indicated only for type 1 diabetes, as clinical trials progress, Eli Lilly may expand its indications to include obesity treatment in the future. Should cell therapy for obesity show advancements, Eli Lilly will also have a pipeline in reserve to address such changes.

Eli Lilly's layout in the weight loss market began as early as 2018, when Eli Lilly paid an initial fee of 50 million US dollars to acquire the global development and commercialization rights of the oral small molecule GLP-1R agonist LY3502970 (Orforglipron) from Chugai.

In order to capture a larger market share, the development of oral GLP-1 drugs has become a new trend. Currently, all marketed GLP-1 agonists are large-molecule peptide analogs, and there are many challenges in developing oral formulations for this class of drugs. Peptides are easily degraded by digestive enzymes and gastric acid, have a short half-life, and exhibit poor gastrointestinal mucosal penetration due to their large molecular size, resulting in low oral bioavailability. In this regard, small-molecule agonists offer clear advantages—they can bypass the technical bottlenecks associated with oral peptide delivery, improve patient compliance, and address absorption and bioavailability limitations at the source, presenting a potentially attractive market.

The foresight and big-picture thinking of large companies are also evident here. As early as 2018, Eli Lilly and Company had already set its sights on the development of oral small-molecule drugs.Strive to ensure that there is no possibility of falling behind in any track with development potential.

On July 14, 2021, Eli Lilly and Company announced a $1 billion acquisition of biotechnology company Protomer Technologies. This deal will give Eli Lilly access to Protomer's engineering platform, which is used to identify and synthesize molecules capable of sensing glucose or other endogenous protein activity modulators, offering potential opportunities for the development of next-generation protein therapies. In the future, Eli Lilly may apply this technology platform to the research and development of drugs for metabolic diseases, including obesity.

"Glucose-sensing insulin is the next frontier, with the potential to revolutionize treatment by enhancing therapeutic efficacy and the safety of insulin therapy, significantly improving the quality of life for people with diabetes," said Ruth Gimeno. "Protomer's glucose-sensing insulin program, based on its proprietary protein-sensing molecular engineering platform, shows great promise, and Eli Lilly and Company is excited to leverage the company's innovative technology to strengthen our product pipeline."

These acquisitions either supplement Eli Lilly's research pipeline or bring in technology platforms to enhance its R&D capabilities. At their core, they all aim to strengthen the company’s core competitiveness and secure a possibility to remain invincible in the ever-changing weight-loss market.

"The three words 'weight-loss drug' have become a symbol of a money-spinning tree, and countless pharmaceutical companies have rushed into this field. Currently, the two super giants in the weight loss market..."Eli Lilly and Novo Nordisk are leading the most cutting-edge competitive trends.However, the development directions of the two companies are slightly different.

Under the full efforts of Novo Nordisk, semaglutide has become a "king-like" presence in the weight loss field. Since then, almost all of Novo Nordisk's actions in the weight loss market have revolved around semaglutide, including "head-to-head" victories over traditional GLP-1 drugs, launching semaglutide tablets to overcome the challenge of oral administration for peptide drugs, and exploring combination therapies based on different doses and product characteristics to expand new indications. Clearly, if Eli Lilly wants to capture a larger share of the weight loss market, a head-to-head comparison with semaglutide is unavoidable.

Different from Novo Nordisk's development model around semaglutide, in the GLP-1 field, Eli Lilly's development strategy is to simultaneously develop new drugs with various mechanisms, starting with GLP-1 drugs, then shifting the focus to dual-target agonists. In the next phase, Eli Lilly will turn its attention to oral small-molecule drugs and triple-target agonists, aiming for a comprehensive and all-encompassing layout.

▲ Eli Lilly's Obesity R&D Pipeline

Eli Lilly's current blockbuster drug is undoubtedly Tirzepatide, which, from its launch in Q2 2022 to Q1 2023, achieved a single-quarter sales revenue of $568.5 million within less than a year on the market. In October 2022, the FDA granted Tirzepatide Fast Track designation for use in adult obesity or overweight.

Eli Lilly's ambition in the weight-loss drug market is directly aimed at Semaglutide. As the "leading contender" with the potential to compete head-to-head with Semaglutide, Eli Lilly has spared no effort to expedite the commercialization of Tirzepatide.

As the announcement of the second Phase III clinical trial results approaches, in order to pave the way for the commercialization of Tirzepatide, Eli Lilly and Company has registered the first Phase IIIb head-to-head study of Tirzepatide versus Semaglutide (2.4mg) for obesity indication, known as the SURMOUNT-5 trial. This study aims to demonstrate the efficacy and safety of Tirzepatide in obese populations without type 2 diabetes, with results expected by early 2025. Additionally, Eli Lilly and Company has two ongoing Phase III clinical trials for Tirzepatide.

From the clinical development history of Tirzepatide, Eli Lilly has focused on proving the superior efficacy of the dual-target mechanism, with semaglutide as its primary benchmark. If Tirzepatide surpasses semaglutide in both efficacy and safety, it will be a crucial step for Eli Lilly to dominate the weight-loss market.

With the continuous emergence of successful cases of single-target drugs, the synergistic advantages of combination targets in weight loss and blood sugar reduction have become increasingly evident. Eli Lilly and Company has also entered the three-target track to gain a competitive edge.

Eli Lilly's triple-target candidate drug Retatrutide shows superior weight-loss capability compared to the dual-target drug Tirzepatide. Results from a Phase II clinical trial involving obese patients without type 2 diabetes indicate that, after 48 weeks of Retatrutide treatment, patients in the highest dose group experienced a 22%-24% reduction in body weight.

In addition to significantly enhancing weight loss effects, another major advantage of Retatrutide is its ability to effectively reduce fatty liver in patients. With the support of multiple indications and treatment scenarios, Retatrutide's competitiveness reaches new heights.

Recently, Eli Lilly and Company registered a series of Phase III clinical trials, including the TRIUMPH-1 and TRIUMPH-2 studies for treating obesity in diabetic and non-diabetic patients, respectively; a clinical trial named TRIUMPH-3 exploring the potential of Retatrutide in obese patients with cardiovascular disease, and the TRIUMPH-4 trial assessing the effects of Retatrutide on obese or overweight patients with knee osteoarthritis.

Globally, the competition in the GLP-1R/GCGR/GIPR triple agonist track is not too intense yet. Currently, only three candidates are in clinical stages, among which only Eli Lilly has progressed to Phase III clinical trials. Novo Nordisk and Sanofi also joined the race but have since withdrawn quietly.

Just as the industry is looking forward to the promising future of Tirzepatide, Eli Lilly and Company has not stopped due to being satisfied with the current situation. Novo Nordisk has already achieved the oral administration of Semaglutide through SNAC technology, and naturally, Eli Lilly does not want to miss the enticing prospects of oral medications in the weight loss market.

Compared with oral peptides, the obvious advantage of Orforglipron is that its administration is not restricted by food or water.

On April 27, Eli Lilly initiated the Phase III ACHIEVE-4 trial of Orforglipron for the treatment of type 2 diabetes and obesity, marking the first registrational clinical trial globally for an oral small-molecule GLP-1 receptor agonist. In May, Eli Lilly launched two Phase III clinical trials for weight loss, ATTAIN-1 and ATTAIN-2, with Orforglipron. On June 28, the clinical trial application for Orforglipron for weight reduction received tacit approval from the CDE.

The rapid clinical trials have positioned Eli Lilly as the global leader in the fastest-progressing oral small molecule agonist space, taking the lead in the oral small molecule赛道. If Phase III clinical data continues to show positive results, Eli Lilly will secure a dominant position in both GLP-1 target injectable drugs and oral small molecule drugs with a promising future, further solidifying its leadership in the weight loss market.

Even if the GLP-1 target has been fully exploited, and Versanis has been acquired to explore new mechanisms for treating obesity, a new modality has already begun to emerge.Perhaps in the near future, we will see Eli Lilly and Company make another move.

On June 24, Fractyl Health, a company focused on pioneering new treatments for type 2 diabetes (T2D) through organ-editing metabolic therapies, presented preclinical findings from its Rejuva program at the 83rd Scientific Sessions/Annual Meeting of the American Diabetes Association (ADA).Highlighted the prospect of the Rejuva platform in reshaping the treatment landscape for type 2 diabetes and obesity through one-time, long-lasting tissue-specific gene therapy.

Rejuva Platform Focuses on Developing Next-Generation AAV-Based Local Delivery Gene Therapies for Type 2 Diabetes and Other Metabolic Disorders. The platform leverages advanced delivery systems and proprietary screening methods to identify and develop pancreatic metabolic-active gene therapy candidates. The project aims to transform the management of metabolic diseases by providing novel disease-modifying therapies that address the root causes of these conditions. Currently, the Rejuva platform is in preclinical development.

Newly Released Breakthrough Results Reveal Stunning Efficacy of Single-Dose GLP-1-Based Gene Therapy Compared to Long-Term Semaglutide Treatment in Diabetic and Obese db/db Rodent Models: A One-Time Pancreatic Gene Therapy (GLP1 PGTx) Reduced Blood Glucose and Total Body Weight by an Additional 54% and 20%, Respectively, Over Long-Term Semaglutide Treatment at 10 nmol/kg/day.

And unlike existing therapies, GLP1 PGTx has the potential to provide lasting therapeutic benefits long after treatment delivery stops, and may offer additional benefits primarily targeting GLP1 within the pancreas.

Professor Geltrude Mingrone of Diabetes and Nutrition at King's College London stated, "We have been looking for a method that can provide efficacy and durability similar to bariatric surgery without undergoing surgery. The results of a single administration of GLP1 PGTx in rodent models indicate that we have discovered a new pathway to achieve this goal, and we look forward to seeing the results of human trials."

Facing its main competitor in the weight-loss market, Novo Nordisk, as well as potential new mechanisms, Eli Lilly and Company continuously seeks breakthroughs within itself, exploring long-term growth points. It has already built a comprehensive product defense system in the weight-loss field, advancing step by step, and constantly evolving.

Looking back at Eli Lilly's layout in the weight loss market, from insulin in the 1920s to the highly successful dulaglutide, even facing formidable competitors like semaglutide, it swiftly responded by launching the powerful Tirzepatide. Meanwhile, more dual-target and triple-target agonists, as well as oral medications, are steadily advancing. This demonstrates that Eli Lilly's success is not merely due to riding a trend but rather the result of long-term dedication to a specific field. With impressive outcomes from self-developed drugs and the acquisition of new therapies to enhance competitiveness, every move and development by Eli Lilly in the weight loss market is highly anticipated.

References:

Eli Lilly to acquire Versanis in heated race for weight loss drugs，STAT

Fractyl Health Demonstrates Significant Improvement in Glucose Control and Obesity in Preclinical Studies of its Rejuva®GLP-1 Based Pancreatic Gene Therapy (GLP1 PGTx) Compared to Chronic Semaglutide at ADA's 83rd Scientific Sessions，Fractyl Health

Lilly to Acquire Versanis to Improve Patient Outcomes in Cardiometabolic Diseases，Lilly

Lilly bets up to $1.9B on Versanis' PhIIb weight loss drug alone and in combo with Novo Nordisk's Wegovy，ENDPOINTSNEWS

Eli Lilly to buy diabetes cell therapy partner Sigilon, expanding bet on preclinical program，ENDPOINTSNEWS

Lilly Spends $1 Billion-Plus on Insulin Innovator Protomer，Biospace