Archive for month: July, 2024

Morphic’s lead program is a selective oral small molecule inhibitor of α4β7 integrin for the treatment of inflammatory bowel disease (IBD) that has the potential to improve outcomes and expand treatment options for patients. This molecule (known as MORF-057) is being evaluated in two Phase 2 studies in ulcerative colitis and one Phase 2 study in Crohn’s disease. Additionally, Morphic is developing a preclinical pipeline of other molecules for the treatment of autoimmune diseases, pulmonary hypertensive diseases, fibrotic diseases and cancer.

“Oral therapies could open up new possibilities for earlier intervention in diseases like ulcerative colitis, and also provide the potential for combination therapy to help patients with more severe disease,” said Daniel Skovronsky, M.D., Ph.D., chief scientific officer of Lilly and president, Lilly Research Laboratories, president, Lilly Immunology. “We are eager to welcome Morphic colleagues to Lilly as this strategic transaction reinforces our commitment to developing new therapies in the field of gastroenterology, where Lilly has made significant investments to deliver first-in-class molecules for the benefit of patients.”

“Morphic has always believed that the immense potential of MORF-057 to benefit patients suffering from IBD could be optimized by the ideal strategic partner. Lilly brings unparalleled resources and commitment to the inflammation and immunology field,” commented Praveen Tipirneni, M.D., CEO of Morphic Therapeutic. “We built the Morphic Integrin Technology platform to realize the vast opportunity of integrin therapeutics. MORF-057 is a tremendous example of those efforts, an oral small molecule α4β7 inhibitor with the potential to be well tolerated and efficacious, attributes that could unlock new possibilities in IBD treatment. My deepest thanks go to the entire Morphic Team for their expertise, creativity and tenacity. We are also grateful to the investigators and patients who have contributed to the success of MORF-057 thus far, and we eagerly anticipate the path forward for MORF-057 and other integrin medicines under Lilly’s stewardship.”

Lilly will commence a tender offer to acquire all outstanding shares of Morphic for a purchase price of $57 per share in cash (an aggregate of approximately $3.2 billion) payable at closing. The transaction has been approved by the boards of directors of both companies.

The transaction is not subject to any financing condition and is expected to close in the third quarter of 2024, subject to customary closing conditions, including the tender of a majority of the outstanding shares of Morphic’s common stock. Following the successful closing of the tender offer, Lilly will acquire any shares of Morphic that are not tendered in the tender offer through a second-step merger at the same consideration as paid in the tender offer.

The purchase price payable at closing represents a premium of approximately 79.0% to the closing stock price on July 5, 2024, and 87.2% to the 30-day volume-weighted average trading price of Morphic’s common stock ended on July 5, 2024, the last trading day before the announcement of the transaction. Morphic’s board of directors recommends that Morphic’s stockholders tender their shares in the tender offer.

Lilly will determine the accounting treatment of this transaction as a business combination or an asset acquisition, including any related acquired in-process research and development charges, according to Generally Accepted Accounting Principles (GAAP) upon closing. This transaction will thereafter be reflected in Lilly’s financial results and financial guidance.

For Lilly, Citi is acting as exclusive financial advisor and Kirkland & Ellis LLP is acting as legal counsel. For Morphic, Centerview Partners LLC is acting as exclusive financial advisor. Evercore Group L.L.C. also provided advice to Morphic. Fenwick & West LLP is acting as legal counsel.

The findings, published in Diabetes Care, suggest hypothalamic inflammation (HI) improvement after bariatric surgery (BS) and may support a role for HI in modulating the weight response to these interventions.

Preclinical studies have linked hypothalamic inflammation to the pathophysiology of obesity and type 2 diabetes. Yet, further research is needed to clarify its significance in disease development and assess its potential for reversal. Considering this, Amanda Jiménez, Endocrinology and Nutrition Department, Hospital Clínic, Barcelona, Spain, and colleagues sought to evaluate the effect of bariatric surgery on radiological HI biomarkers and the association between the severity of such radiological alterations and post-BS WL trajectories. They also explored the utility of cerebrospinal fluid large extracellular vesicles (CSF-lEVs) enriched for microglial and astrocyte markers in studying HI.

The researchers included 72 individuals with obesity (20 with and 52 without type 2 diabetes) and 24 control individuals. Participants underwent lumbar puncture and underwent a 3-T MRI at baseline and again at 1-year post-bariatric surgery. The research team assessed hypothalamic mean diffusivity (MD) (higher values indicate lesser microstructural integrity) and the volume of the whole and main hypothalamic subregions. Flow cytometry determined CSF-lEVs enriched for astrocyte and glial markers.

The study led to the following findings:

• The obesity and type 2 diabetes groups showed a larger volume and higher MD in the hypothalamic tubular inferior region, the area encompassing the arcuate nucleus, compared with the control group. These radiological alterations were positively associated with baseline anthropometric and metabolic measures and improved post-BS.
• A larger baseline tubular inferior hypothalamic volume was independently related to lesser WL 1 and 2 years after BS.
• CSF-lEVs did not differ among groups and were unrelated to WL trajectories.

“This study proposes that individuals with obesity and type 2 diabetes exhibit hypothalamic inflammation, which could influence the weight-loss outcomes observed after undergoing bariatric surgery,” the researchers wrote.

In conclusion, the study underscores the dual benefits of bariatric surgery in reducing hypothalamic inflammation and predicting short-term weight loss outcomes. These findings advance understanding of the neurobiological mechanisms underlying obesity and also offer potential avenues for personalized treatment strategies aimed at improving metabolic health in adults with or without type 2 diabetes.

Reference:

Adriana Pané, Laura Videla, Àngels Calvet, Judith Viaplana, Lídia Vaqué-Alcázar, Ainitze Ibarzabal, Mateus Rozalem-Aranha, Jordi Pegueroles, Violeta Moize, Josep Vidal, Emilio Ortega, Isabel Barroeta, Valle Camacho, Gemma Chiva-Blanch, Juan Fortea, Amanda Jiménez; Hypothalamic Inflammation Improves Through Bariatric Surgery, and Hypothalamic Volume Predicts Short-Term Weight Loss Response in Adults With or Without Type 2 Diabetes. Diabetes Care 20 June 2024; 47 (7): 1162–1170. https://doi.org/10.2337/dc23-2213

Previous clinical trials established the efficacy of ICDs in reducing sudden cardiac death among high-risk patients. However, since those studies, there have been notable advancements in heart failure (HF) treatment and ICD technology, necessitating an updated evaluation of ICD benefits.

The primary aim of this study was to compare mortality rates between patients with a primary prevention indication for an ICD who received the device and those who did not, using contemporary real-world data. The study analyzed data from a large electronic health record database of U.S. patients between 2012 and 2020. Included patients had a PP indication for ICD and survived at least one year post-indication.

The study findings were as follows:

• A total of 25,296 patients met the inclusion criteria. Among them, 2,118 (8.4%) received an ICD within a year of indication.

• The treated group was younger (average age 63.4 years) compared to the non-treated group (average age 66.1 years) and had a smaller proportion of women (25.0% vs 36.7%).

• After adjusting for clinical characteristics through 4-to-1 propensity matching, the study employed a Cox proportional hazard model to estimate the impact of ICD treatment on mortality.

• Patients treated with an ICD had a 24.3% lower risk of all-cause mortality compared to those who did not receive the device (HR: 0.757; 95% CI: 0.678-0.835; P < 0.001).

• There was no significant difference in ICD benefit between patients with ischemic and nonischemic heart disease (P = 0.50).

The absence of differential benefit between ischemic and nonischemic heart disease patients suggests a broad applicability of ICDs across different heart failure etiologies. ICD therapy for patients with a primary prevention indication is associated with a significant reduction in all-cause mortality.

Reference:

Ahmed, A., Auricchio, A., Mittal, S., Pickett, R. A., Wilkoff, B. L., Jacobsen, L. D., Marti, A. K., Holbrook, R. W., Soderlund, D. M., & Curtis, A. B. (2024). Mortality benefit among primary prevention implantable cardioverter-defibrillator recipients on contemporary heart failure treatment. JACC. Clinical Electrophysiology, 10(5), 916–926. https://doi.org/10.1016/j.jacep.2024.102334