▎WuXiEdited by Kant Content Team

Recently, the global peptide and oligonucleotide (TIDES) field has welcomed a seriesProgress. The world's first telomerase inhibitorRytelo（imeteLstat) has been approved for marketing in Europe, becoming the first telomerase inhibitor to be approved in both the United States and Europe.Johnson & Johnson for the treatment ofPlaque Psoriasis (PsO)Oral PolypeptidePositive Results from Multiple Phase 3 Clinical Trials of Icotrokinra. Roche and Zealand Pharma have reached a global collaboration and licensing agreement worth over $5 billion to jointly develop Zealand's amylin analog petrelintide as a cornerstone therapy for weight management.

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Rytelo（imetelstat): Approved for marketing by the European Commission

Geron Corporation announced that the European Commission (EC) has approved its telomerase inhibitor Rytelo (imetelstat) as a monotherapy,For the treatment of transfusion-dependent anemia in adult patients caused by very low-risk, low-risk, or intermediate-risk myelodysplastic syndromes. These patients do not have deletion of the long arm of chromosome 5 (non-del 5q).CytogeneticsAbnormal, and the patient does not respond to or has developed resistance to erythropoiesis-stimulating agents (ESAs), or is not suitable for ESA use.In June 2024, the U.S. FDA hadApprovalThe therapy is launched.The press release pointed out,RyteloIt is the first telomerase inhibitor approved in the United States and Europe.

Rytelo is a "first-in-class" oligonucleotide telomerase inhibitor.Telomeres are protective caps at the ends of chromosomes that naturally shorten with each cell division. In low-riskMyelodysplastic Syndromes (MDS)In China, abnormal bone marrow cells typically express telomerase, which rebuilds telomeres, leading to uncontrolled cell division.Preclinical and clinical trial data show that Rytelo, by inhibiting telomerase activity, can suppress the uncontrolled proliferation of cancerous stem cells and progenitor cells, leading to the apoptosis of cancerous cells, and has the potential to alter disease progression.

Icotrokinra (JNJ-2113): Phase 3 Clinical Trial Data Released

Johnson & Johnson announced positive topline results from its pivotal Phase 3 study, ICONIC-LEAD, and launched the first head-to-head study comparing icotrokinra with the injectable biologic ustekinumab for the treatment of moderate to severe plaque psoriasis. According to the press release,Icotrokinra is the first targeted oral peptide under investigation aimed at blocking IL-23R.Currently being evaluated in adults and adolescents aged 12 years and older with moderate to severe PsO.Icotrokinra can bind to IL-23R with single-digit picomolar affinity and exerts potent selective inhibition of IL-23 signaling in human T cells.

The analysis shows,Once-daily icotrokinra significantly improved skin condition in patients with moderate to severe plaque psoriasis and demonstrated a favorable safety profile.At week 16, 65% of patients in the icotrokinra group achieved an Investigator Global Assessment (IGA) score of 0/1 (clear or almost clear skin symptoms), and 50% achieved at least a 90% improvement in the Psoriasis Area and Severity Index (PASI 90), compared to only 8% and 4% in the placebo group for these two metrics respectively. By week 24, the patient response rate further improved, with 74% achieving an IGA score of 0/1, 46% achieving an IGA score of 0; 65% achieving PASI 90, and 40% achieving PASI 100. In terms of safety, the incidence of adverse events (AE) at week 16 was similar between the icotrokinra and placebo groups, both at 49%, with no new safety signals identified.

In addition, the results of the Phase 3 ICONIC-ADVANCE 1&2 studies showed,Icotrokinra achieved the co-primary endpoints and outperformed the active comparator TYK2 inhibitor in treating moderate to severe PsO.These results pave the way for the subsequent initiation of the first head-to-head study with the IL-12 inhibitor ustekinumab.

ARO-C3: New Data from Phase 1/2 Clinical Trial Released

Arrowhead Pharmaceuticals Announces Part 2 Data from Phase 1/2 Clinical Trial of Investigational RNAi Therapy ARO-C3. Complement-mediated diseases include IgA nephropathy, C3 glomerulopathy, paroxysmal nocturnal hemoglobinuria, and other renal and hematological indications. Although therapies targeting the C5 protein have been approved and launched, this field still has unmet medical needs.ARO-C3 is an RNAi therapy targeting the complement protein C3, which inhibits the expression of the C3 protein by binding to the mRNA encoding the C3 protein.Since the C3 protein is upstream of the C5 protein in the complement signaling pathway, Arrowhead believes it has potential in treating various complement-mediated diseases.

The data released this time show that ARO-C3 can sustainably and significantly reduce the activity of the complement alternative pathway and proteinuria.Patients with Immunoglobulin A Nephropathy (IgAN) experienced an average sustained reduction of ≥87% in C3 levels from baseline by Week 24 of treatment, an average sustained decrease of ≥76% in serum AH50 (alternative pathway hemolysis assay), an average sustained reduction of ≥89% in Wieslab AP (a test assessing alternative pathway activity), and an average decline of 41% in the Urine Protein-to-Creatinine Ratio (UPCR).In terms of safety, ARO-C3 was well-tolerated in patients with IgAN, with no serious treatment-emergent adverse events (TEAEs), and no TEAEs leading to study discontinuation or drug withdrawal.

Roche Collaborates to Develop Potential "Best-in-Class"Amylin Analogues

Zealand Pharma recently announced a global collaboration and licensing agreement with Roche to jointly develop Zealand Pharma's amylin analog, petrelintide., as a cornerstone therapy for weight management, while rapidly expanding to related indications. The press release noted,Petrelintide has the potential to become a "best-in-class" therapy.

According to the agreement,The two parties will jointly develop and commercialize petrelintide and its combination products, including a fixed-dose combination product of petrelintide with Roche's potential "best-in-class" glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor dual agonist CT-388.Both parties will jointly commercialize petrelintide and other products generated from this collaboration in the United States and Europe, while Roche obtains exclusive commercialization rights in the rest of the world. Zealand Pharma can participate in up to 50% of commercialization activities in the United States and Europe.

Zealand Pharma to Receive $1.65 Billion Upfront Payment. Zealand Pharma is Also Eligible for $1.2 Billion in Development Milestone Payments (Primarily Related to the Phase 3 Clinical Trial Initiation of Petrelintide Monotherapy) and $2.4 Billion in Sales Milestone Payments.

Petrelintide is a long-acting amylin analog suitable for once-weekly subcutaneous injection.This drug was designed with an emphasis on chemical and physical stability, showing no fibrillation at neutral pH, thus allowing for combination formulations and co-administration with other peptide drugs.

Limited by space,This article only provides a brief introduction to some significant advancements.。Readers are welcome to long press/scan the following QR code to apply for the "TIDES Therapy Progress Review, March 2025, Issue 2" containing complete table summaries.

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[1] Arrowhead Pharmaceuticals Announces Topline Results from Part 2 of Phase 1/2 Study of ARO-C3 in Patients with IgA Nephropathy. Retrieved March 14, 2025, from https://ir.arrowheadpharma.com/news-releases/news-release-details/arrowhead-pharmaceuticals-announces-topline-results-part-2-phase

[2] Icotrokinra results show potential to set a new standard of treatment in plaque psoriasis. Retrieved March 14, 2025, from https://www.jnj.com/media-center/press-releases/icotrokinra-results-show-potential-to-set-a-new-standard-of-treatment-in-plaque-psoriasis

[3] Geron Announces European Commission Approval of RYTELO® (imetelstat), a First-in-Class Telomerase Inhibitor, for the Treatment of Adults With Transfusion-Dependent Anemia Due to Lower-Risk MDS. Retrieved March 14, 2025, from https://ir.geron.com/investors/press-releases/press-release-details/2025/Geron-Announces-European-Commission-Approval-of-RYTELO-imetelstat-a-First-in-Class-Telomerase-Inhibitor-for-the-Treatment-of-Adults-With-Transfusion-Dependent-Anemia-Due-to-Lower-Risk-MDS/default.aspx

[4] Zealand Pharma and Roche enter collaboration and license agreement to co-develop and co-commercialize petrelintide as a future foundational therapy for people with overweight and obesity. Retrieved March 12, 2025, from https://www.globenewswire.com/news-release/2025/03/12/3041113/0/en/Zealand-Pharma-and-Roche-enter-collaboration-and-license-agreement-to-co-develop-and-co-commercialize-petrelintide-as-a-future-foundational-therapy-for-people-with-overweight-and-o.html