Menten AI and BMS Partner to Accelerate Macrocyclic Peptide Design Using Generative AI

01

2024-5-28, Henry Meds, dedicated to patient-centered care, announced the launch of a compound oral dissolving Tirzepatide tablet. This breakthrough oral dissolving tablet enhances patient medication adherence. Henry Meds has specifically partnered with licensed compounding pharmacies, which source active pharmaceutical ingredients from FDA-registered suppliers. The active ingredient is identical to that of Lilly's Mounjaro® and Zepbound®. Tirzepatide has demonstrated significant efficacy in supporting weight loss. By enhancing insulin production, reducing glucagon secretion, and regulating appetite-regulating brain regions, Tirzepatide provides comprehensive support for individuals pursuing a healthier lifestyle.

Among them, Henry Meds is a leading telemedicine platform dedicated to revolutionary healthcare services. Through innovation and a commitment to patient-centered care, Henry Meds enables individuals to affordably and conveniently access high-quality healthcare solutions.

02

2024-5-28, selectION, an expert in developing new therapies for T cell-mediated autoimmune diseases, announced the launch of a Phase Ib clinical trial to evaluate the efficacy of si-544 in patients with plaque psoriasis or psoriatic arthritis. Recruitment is currently underway, with top-line data expected to be released in Q4 2024.

The trial showed that si-544 demonstrated excellent safety and tolerability, with preliminary efficacy signals observed. Previously, si-544 also exhibited superior efficacy in animal and human T-cell models.

Among them, si-544 is a peptide candidate drug that selectively blocks the ion channel Kv1.3, functionally inhibiting and eliminating disease-specific, chronically activated TEM cells while maintaining full immune activity. TEM cells are the root cause of many autoimmune conditions, such as atopic dermatitis, psoriasis, rheumatoid arthritis, or multiple sclerosis, as well as certain rare cancers like lymphoma.

Moreover, selectION is a clinical-stage biopharmaceutical company developing novel peptide therapies for autoimmune diseases and specific cancer indications by targeting self-reactive, chronically activated T cells. The company has built an efficient and unique technology platform to develop potent and highly selective peptide blockers for ion channels involved in various diseases. This platform enables the systematic optimization of target selectivity, providing opportunities to develop drugs with significantly improved efficacy and safety.

03

2024-5-28, BoAn Biologics, a company dedicated to the development, manufacturing, and commercialization of biopharmaceuticals, announced that the marketing application (BLA) for its self-developed Dulaglutide Injection (BA5101) has been accepted by the CDE.

Among them, BA5101 is the first biosimilar of Trulicity® in China to have submitted an application for marketing authorization, intended for glycemic control in adult patients with type 2 diabetes. The international registration and clinical trials of this product are also being actively advanced. The development process of BA5101 strictly adheres to the relevant biosimilar research guidelines in China, the United States, and the European Union. Both pivotal clinical studies comparing it with the originator reference drug met all endpoints: Phase I clinical trials demonstrated that BA5101 has highly similar PK characteristics, safety, and immunogenicity to Trulicity®. Relevant research findings were published in the international academic journal *Expert Opinion on Biological Therapy*. Phase III clinical trials confirmed that BA5101 can rapidly and stably reduce blood glucose and glycated hemoglobin, with efficacy and safety consistent with Trulicity®.

Dulaglutide is a long-acting GLP-1 (glucagon-like peptide-1) receptor agonist administered once weekly. Compared with other types of hypoglycemic agents, Dulaglutide improves the function of pancreatic β-cells, providing stable and effective reduction of blood glucose and glycated hemoglobin (HbA1c) levels. Additionally, its unique mechanism of action is less likely to cause hypoglycemia and can reduce body weight, lipid levels, and the long-term risk of cardiovascular diseases, while also offering protective effects on the kidneys. Multiple clinical studies have also shown that the once-weekly dosing regimen of Dulaglutide reduces the inconvenience of medication for patients, leading to higher medication adherence.

Among them, BoAn Biotech (6955.HK) is a fully integrated biopharmaceutical company specializing in the development, production, and commercialization of biologics, with a focus on oncology, autoimmune diseases, ophthalmology, and metabolic disorders. The company’s new drug discovery activities are centered around multiple platforms, including a fully human antibody transgenic mouse and phage display technology platform, a bispecific T-cell engager technology platform, an antibody-drug conjugate (ADC) technology platform, and a cell therapy platform.

04

On 2024-5-28, the majority of the FDA advisory panel members evaluated the risks and benefits of Novo Nordisk's once-weekly insulin icodec and concluded that the benefits did not significantly outweigh the risks.

Among the 11 voting members of the Endocrinology and Metabolism Drugs Advisory Committee meeting, 7 members disagreed that the benefits outweighed the risks, while 4 members agreed.

Briefing documents provided by FDA scientists showed that in a key trial, icodec insulin, injected once a week, presented hypoglycemia issues compared to Novo Nordisk's once-daily Tresiba (insulin degludec), which raised concerns among several expert panel members. Several experts stated that icodec insulin might be suitable for some patients, but Novo Nordisk needs to specify which patient populations these are.

05

On May 28, 2024, Vasomune Therapeutics, dedicated to developing a new generation of drugs, announced that the FDA had granted AV-001 Fast Track designation.

AV-001 is a first-in-class, fully synthetic pegylated peptide, a novel investigational drug targeting the Tie2 receptor, which is the most strongly expressed transmembrane protein on the surface of endothelial cells in the vasculature. AV-001 activates the non-redundant Tie2-angiopoietin signaling axis and normalizes the vasculature by stimulating multiple downstream pathways, enhancing endothelial cell stability, restoring normal barrier defenses, and blocking vascular leakage. Vascular dysfunction can contribute to the underlying pathophysiology of diseases such as bacterial and viral acute respiratory distress syndrome, sepsis, hemorrhagic shock, acute kidney injury, stroke, and vascular dementia. Importantly, in multiple preclinical studies, AV-001 tightened endothelial cell-cell junctions and promoted endothelial cell survival, reducing pulmonary edema and improving lung function compared to untreated controls, significantly increasing survival rates.

Among them, Vasomune Therapeutics is a private clinical-stage biopharmaceutical company dedicated to developing a new generation of drugs that leverage the body's ability to fight disease. Established in 2014, the company focuses on vascular normalization drug development strategies and has advanced its lead candidate, AV-001, from the lab to clinical trials.

06

2024-5-29, Guangzhou Yuheng Biotechnology Co., Ltd., dedicated to tumor immunotherapy, announced that its CXCR4 antagonist Motixafortide (BL-8040) has been approved by the CDE for a Phase III clinical study in hematopoietic stem cell transplantation.

Based on the expectation of no ethnic differences in the Asian subject data from the global multicenter Phase III GENESIS clinical trial, which has received marketing approval, the approval in China this time is for a randomized, double-blind, placebo-controlled multicenter bridging Phase III clinical study. The GENESIS study was led by the University of Washington in the United States, which performed the world’s first hematopoietic stem cell transplant. The results showed that 92.5% of patients in the Motixafortide+G-CSF group successfully reached the primary endpoint with a single injection and up to two collections, meaning 92.5% of patients were able to collect the ideal number of stem cells (6 × 10^6 CD34+ cells/kg). The median number of cells collected in a single apheresis was five times that of using G-CSF alone (~11M vs ~2M), ensuring the necessary cell count for autologous hematopoietic stem cell transplantation, with good safety. The results of the GENESIS study were published in April 2023 in the journal *Nature Medicine*.

Among them, Motixafortide is an innovative cyclic peptide CXCR4 antagonist administered via subcutaneous injection. It has high affinity, binding to the CRCX4 receptor at six sites, with an effect lasting more than 72 hours. It has been verified to efficiently mobilize stem cells from the bone marrow to the peripheral blood.

01

2024-5-28, Menten AI, dedicated to designing a new generation of cyclic peptide therapies, announced a collaboration with BMS to accelerate the design and optimization of macrocyclic peptides using Menten AI's generative AI platform.

In the research collaboration, Menten AI and BMS leverage Menten AI's generative AI platform and the team’s expertise to optimize the biochemical properties of certain macrocyclic peptides. The team will jointly explore a broader chemical space and identify new amino acid modifications to enhance desired characteristics.

Among them, Menten AI is developing generative AI to design a new generation of cyclic peptide therapies, targeting drug targets that small molecules and biologics cannot reach. Their proprietary platform can design effective and membrane-permeable macrocyclic peptides within weeks. The team has already validated their complex drug target platform both in vitro and in vivo, including protein-protein interfaces (PPIs). The company has established partnerships with top 10 pharmaceutical companies to support and accelerate their preclinical drug discovery efforts. Menten AI is backed by top venture capital firms, including Social Impact Capital, Uncork Capital, Khosla Ventures, and Y-Combinator.

02

2024-5-28, Imagine Pharma, dedicated to advancing the commercialization of its novel IMG-1 peptide in oral drug delivery, therapeutic, and regenerative medicine fields, announced that West Virginia University (WVU) Health System, operating under the WVU Medicine brand, has signed a contract with the company to provide clinical islet isolation services for patients undergoing total pancreatectomy and autologous islet cell transplantation (TPAIT).

Among them, TPAIT is a surgical procedure used to remove the diseased pancreas, harvest the insulin-secreting islet cells from the pancreas, and then reinfuse or transplant these cells back into the patient’s body to control blood sugar. Pancreatectomy without islet transplantation can lead to diabetes or the inability to regulate blood sugar.

Among them, Imagine Pharma is a biotechnology company focusing on the development of its IMG-1 peptide. The company has built three unique platforms: oral drug delivery, therapeutics, and regenerative medicine. Each platform features a "First in Class" project that can be utilized to develop drugs for various diseases addressing large, underserved markets. Imagine Pharma was recently selected as part of the comprehensive islet distribution program of the Islet Cell Resource Center approved by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in the United States.

03

2024-5-28, BioLineRx, a clinical-stage biopharmaceutical company focused on cancer drug development, announced its Q1 2024 financial report and latest corporate updates.

In 2024 Q1, total revenue was $6.9Mn, cost of revenue was $1.5Mn, R&D expenses were $2.5Mn, sales and marketing expenses were $6.3Mn, administrative expenses were $1.4Mn, non-operating income was $4.5Mn, financial income was $0.6Mn, financial expenses were $0.9Mn, and the total net loss was $0.7Mn.

Moreover, APHEXDA® has seen steady sales growth in Q1 post-approval. To date, approximately 26% of the top 80 transplant centers have adopted APHEXDA prescriptions for transplantation, with expectations to reach the established goal of around 35% by Q2. Additionally, $26 million in debt and equity financing was completed in Q1 to support APHEXDA’s commercialization and business expansion in the U.S. Partner Gloria Biosciences’ motixafortide HSC mobilization bridging study IND has been approved by the CDE, with clinical trials anticipated to commence in H2 2024.

04

On May 28, 2024, Secarna Pharma, a leader in antisense drug discovery and development, and Orbit Discovery, a leader in therapeutic peptide target discovery, announced a collaboration to discover and develop peptide-conjugated targeted antisense oligonucleotide (POC) therapies.

This collaboration will leverage Orbit's expertise and bead-based display technology to identify, screen, and select cyclic peptides targeting various disease targets, pairing them with Secarna’s ASO molecules. The addition of cyclic peptides to Secarna's proprietary ASO discovery and development platform will expand its therapeutic scope, enabling the development of targeted ASO assets beyond antibody and glycan (e.g., GalNAc) conjugation modalities.

Among them, Orbit's peptide discovery service, by combining DNA-encoded libraries with bead-based display technology, is capable of screening large peptide libraries. This proprietary technology has the unique ability to address soluble targets and targets in situ, whether on or within cells, enabling the faster discovery of relevant peptide leads through affinity-based and/or functional screening.

05

On May 31, 2024, Zealand Pharma, a company focused on discovering and developing innovative peptide drugs, announced that the CHMP of the EMA recommended the approval of Dasiglucagon injection for marketing in the EU.

Dasiglucagon Injection was approved by the FDA on March 22, 2021, and launched under the brand name Zegalogue® for the treatment of severe hypoglycemia in patients with diabetes aged 6 years and older. Zegalogue® is available in the United States in both autoinjector and prefilled syringe forms. The FDA approval was based on the results of three pivotal trials involving adults and children with diabetes, which showed that the median time to recovery from severe hypoglycemia after injecting 0.6mg/0.6mL of Dasiglucagon was 10 minutes. In these Phase III trials, the most common adverse events reported (≥2%) were nausea, vomiting, headache, diarrhea, and injection site pain in adults; and nausea, vomiting, headache, and injection site pain in pediatric patients.

Among them, Zealand Pharma is a biotechnology company focused on the discovery and development of peptide drugs. Established in 1998, the company is headquartered in Copenhagen, Denmark, with offices in the United States. More than 10 of its invented drug candidates have entered the clinical development stage, two of which are already on the market, and three drug candidates are in the late-stage development phase. The company has established development partnerships with multiple pharmaceutical companies and commercial partnerships for its marketed products.

01

On 2024-5-30, Bradley L. Pentelute from MIT and Aaron H. Nile from Calico Life Science published an article entitled "Reversibly Reactive Affinity Selection−Mass Spectrometry Enables Identification of Covalent Peptide Binders".

The article points out: To develop peptide-based drugs targeting specific proteins, rational design based on the structure of the target protein or screening from libraries using technologies such as phage display and mRNA display can be employed. Peptide binders discovered through these methods typically exhibit micromolar affinity. Based on the identified peptide binders, a peptide library can be designed and synthesized, and screening from this library can effectively enhance the affinity of the identified peptides. Previously, the Pentelute group developed an affinity selection-mass spectrometry platform in solution that is capable of screening peptide binders with mid-to-low nanomolar affinity. Adding a covalent warhead to peptide binders is an effective approach to address their rapid degradation and short circulation time. Therefore, the authors of this article have developed a method for screening peptide binders from large synthetic non-canonical peptide libraries.

In the article, the author reported the screening strategy of this platform as follows: For a single protein, a peptide library was designed and synthesized based on its known binding peptides. The peptides in the library carry a covalent warhead of mercaptoethylamine, which can form a disulfide bond with the Cys of the protein. After incubation of the peptide library with the protein, size exclusion chromatography was used to remove the peptides that did not bind to the protein. Then, DTT was used to release the peptides bound to the protein, which were then sent for mass spectrometry detection to identify potential covalent peptides that bind to the protein. These peptides were subsequently modified by replacing the reversible mercaptoethylamine warhead with chloroacetyl or Dha to obtain the final covalent peptides. The article mainly verified the feasibility of this platform on two proteins, PV16 E6 and Pin1.