$600M Deal: Novo Nordisk Partners Again with Flagship to Develop GLP-1 Multi-Target Long-Acting Therapies for Weight Loss

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On May 9, 2024, Innovent Bio announced that the Phase III clinical trial (DREAMS-2) of its dual agonist of glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR), Mazdutide (research code: IBI362), conducted among Chinese patients with type 2 diabetes, has met the primary endpoint. The study results indicate that Mazdutide demonstrates significantly superior glucose-lowering efficacy compared to Dulaglutide and shows more comprehensive benefits across metabolic indicators such as weight loss, lipids, blood pressure, serum uric acid, and liver enzymes.

DREAMS-2 (NCT05606913) is a multicenter, randomized Phase III clinical study comparing the efficacy and safety of Masitide and Dulaglutide in Chinese subjects with type 2 diabetes whose blood glucose was poorly controlled by metformin monotherapy or combination therapy with other oral medications. The study enrolled 731 subjects who were randomly assigned to receive either Masitide 4.0 mg, Masitide 6.0 mg, or Dulaglutide 1.5 mg for a total of 28 weeks. The primary endpoint of the DREAMS-2 study is the change in glycated hemoglobin (HbA1c) from baseline; the study uses a non-inferiority design, followed by a superiority test after achieving non-inferiority.

After 28 weeks of treatment, the improvement in HbA1c from baseline with MASHIDUO PEPTIDE 4.0 mg and MASHIDUO PEPTIDE 6.0 mg was non-inferior to that of Dulaglutide 1.5 mg. Furthermore, upon subsequent superiority testing, both MASHIDUO PEPTIDE 4.0 mg and 6.0 mg demonstrated superior glucose-lowering effects compared to Dulaglutide 1.5 mg.

After 28 weeks of treatment with MASHIDUPEPTIDE 4.0 mg and MASHIDUPEPTIDE 6.0 mg, the change in HbA1c from baseline (superiority), the percentage change in body weight from baseline, the proportion of subjects with HbA1c <7.0% and body weight reduction ≥5% from baseline, and the proportion of subjects with HbA1c <7.0% all achieved statistical superiority*. The drug showed good safety and tolerability without additional safety signals.

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2024-5-6, AsclepiX Therapeutics, a clinical-stage biotechnology company leveraging computational biology from Johns Hopkins University to identify and develop peptides for improving the treatment of retinal diseases, announced the completion of enrollment for the DISCOVER trial (NCT05859776).

15 Patients Have Completed Enrollment in the AXT107 (Gersizangitide) Trial. The purpose of the trial is to evaluate the safety and tolerability of three dose levels of AXT107 [125 μg (n=3), 250 μg (n=3), and 500 μg (n=9)] and to determine the biological activity and duration of effect following suprachoroidal injection. Secondary endpoints will include efficacy assessments via central subfield thickness (CST) and best-corrected visual acuity (BCVA). To date, following a single injection of AXT107, no patients have exhibited any significant safety findings.

Among them, AXT107 inhibits pro-angiogenic vascular endothelial growth factor receptor 2 (VEGFR2) and activates vascular stabilization receptor tyrosine kinase (Tie2), which are two effective pathways for treating retinal vascular diseases. Both pathways are mediated by the interaction of AXT107 with integrin αvβ3 and integrin α5β1. AXT107 is a microparticle suspension suitable for intravitreal injection.

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2024-5-9, Flagship Pioneering and its subsidiary Metaphore Biotechnologies jointly announced that Metaphore has reached a strategic collaboration with Novo Nordisk to co-develop up to two next-generation obesity treatment drugs.

This collaboration falls under the broader strategic partnership between Novo Nordisk and Flagship Pioneering, which aims to jointly develop novel therapeutic solutions for cardiometabolic diseases and rare disorders. Pioneering Medicines, Flagship's internal drug development and collaboration unit, and Novo Nordisk’s Bio Innovation Hub will co-lead this partnership to develop up to two next-generation weight loss therapies. Metaphore, Pioneering Medicines, and Novo Nordisk will collaborate on foundational research and preclinical development, after which Novo Nordisk will advance these programs into clinical trials.

Under the terms of the agreement, Novo Nordisk may pay up to $600 million in upfront, development, and commercial milestone payments, as well as tiered royalties on annual net sales of licensed products, to be shared by Metaphore and Pioneering Medicine. Novo Nordisk will also reimburse R&D costs and participate in Metaphore's future financing.

This collaboration will leverage Metaphore's MIMIC platform to design multi-target therapies aimed at the GLP-1 receptor and related biology, with the goal of developing long-acting drugs that do not require frequent administration. Metaphore will partner with Pioneering Medicines and Novo Nordisk to advance the project through foundational research and preclinical development, after which Novo Nordisk can move the project into clinical studies.

Metaphore is the third biotechnology company incubated by Flagship Pioneering after Omega Therapeutics and Cellarity, and it has also reached a collaboration with Novo Nordisk. This marks a further deepening of the strategic research and development collaboration between Novo Nordisk and Flagship on cardiovascular, metabolic, and rare disease drugs.

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Xianweda Bio Announces Collaboration with Hk Inno.N, a Subsidiary of Kolmar Group (Kolmar, KRX:161890), South Korea's Leading Consumer Healthcare Company, for the Licensing of Ecnoglutide’s Rights in South Korea. Hk Inno.N will be responsible for clinical development and commercialization in the region. Under the agreement, Xianweda will receive upfront and milestone payments totaling nearly $60 million, along with double-digit royalties on net sales during subsequent commercialization. HK inno.N Corporation will obtain exclusive rights to develop and commercialize Ecnoglutide in the Republic of Korea. Xianweda retains the rights to develop and commercialize Ecnoglutide in all other global markets.

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Tonghua Dongbao and Zhibio Sign "Commercial Authorization and MAH Cooperation Agreement" for GLP-1 Product Semaglutide Injection. According to the agreement, Tonghua Dongbao will obtain exclusive commercial rights in mainland China for Zhibio's clinical-stage product ZT001 Semaglutide Injection (Indication: Blood glucose control in adult patients with type 2 diabetes) as well as the right to jointly develop overseas markets. The cooperative product has completed Phase I clinical trials for type 2 diabetes indications in mainland China and has initiated Phase III clinical research.

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According to the latest news from Endpoints News, Eternity Biopharma plans to go public on Nasdaq in early 2025, with a potential crossover round of financing before that. "The U.S. general election is underway in the second half of the year, and we are also keeping an eye on interest rate changes. The IPO actually depends on market conditions, and we believe early next year will be a good opportunity for the company," said Zhou Jingye, CEO of Eternity Biopharma. "Once the market opens up opportunities, we will spare no effort."

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Recently, Simon Harrisson and Colin Bonduelle from the University of Bordeaux published an article titled "Toward Synthetic Intrinsically Disordered Polypeptides (IDPs): Controlled Incorporation of Glycine in the Ring-Opening Polymerization of N‑Carboxyanhydrides" in Biomacromolecules.

The article points out that intrinsically disordered proteins (IDPs) lack secondary structures and behave as free polymer chains in solution; however, they play important structural and functional roles in living organisms. IDPs are mainly composed of random coil segments and typically exhibit high solubility and low aggregation propensity. On one hand, the widespread presence of polar amino acids promotes chain solvation, while charged residues create repulsion between segments. On the other hand, the frequent occurrence of proline and glycine in the structure can also disrupt secondary structures.

Polymerized polypeptides with randomly distributed amino acids are macromolecules simpler than proteins, combining the advantages of both synthetic polymers and natural proteins. Polypeptides are typically synthesized through the ring-opening polymerization of N-carboxyanhydrides (NCAs), and the distribution of monomers significantly influences the polymer’s properties. However, relatively fewer studies have focused on the copolymerization kinetics of NCAs to control the primary sequence of polypeptides and its impact on secondary structures.

The author of this article studied the kinetics, reactivity ratios, monomer distribution, and secondary structure of the copolymerization of BLG-NCA and Gly-NCA. The author found that the helical conformation could be disrupted by controlling reactivity and the addition of glycine, resulting in a chiral poly(γ-benzyl-L-glutamate) with a helix-disordered state, which is an intrinsically disordered polypeptide. DMSO was the optimal solvent for the reaction, where the formation of high-gradient copolymer microstructures could be observed.