A Phase 3, Parallel-group, Randomized, Double-blind, 4-arm, Placebo-controlled, Multicenter Study with Risankizumab As Active Reference Arm, to Investigate the Efficacy and Safety of Subcutaneous Sonelokimab in Male and Female Participants Aged 18 Years and Over with Active Psoriatic Arthritis and Previous Inadequate Response or Intolerance to Tumor Necrosis Factor-α Inhibitors

This is a study to confirm the clinical efficacy and safety of sonelokimab compared with placebo in the treatment of adults with active psoriatic arthritis who have had a previous inadequate response or intolerance to anti-tumor necrosis factor (TNF)α therapy.

开始日期2024-10-15

申办/合作机构

MoonLake Immunotherapeutics

NCT06641076 / Not yet recruiting临床3期

A Phase 3, Parallel-group, Randomized, Double-blind, 3-arm, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of Subcutaneous Sonelokimab in Male and Female Participants Aged 18 Years and Over with Active Psoriatic Arthritis Who Are Naive to Biologic DMARDs

This is a study to demonstrate the clinical efficacy and safety of sonelokimab administered subcutaneously compared with placebo in the treatment of adult patients with active psoriatic arthritis who are naive to biologic disease-modifying antirheumatic drug therapy.

开始日期2024-10-15

申办/合作机构

MoonLake Immunotherapeutics

CTIS2024-511363-28-00 / Recruiting

A phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of subcutaneous sonelokimab in adult participants with moderate to severe hidradenitis suppurativa (M1095-HS-302) - M1095-HS-302

开始日期2024-09-24

申办/合作机构

MoonLake Immunotherapeutics

100 项与 IL-17A x albumin x IL-17F 相关的临床结果

登录后查看更多信息

100 项与 IL-17A x albumin x IL-17F 相关的转化医学

登录后查看更多信息

0 项与 IL-17A x albumin x IL-17F 相关的专利（医药）

登录后查看更多信息

项与 IL-17A x albumin x IL-17F 相关的文献（医药）

2021-04-01·The Lancet1区 · 医学

IL17A/F nanobody sonelokimab in patients with plaque psoriasis: a multicentre, randomised, placebo-controlled, phase 2b study

1区 · 医学

Article

作者: Weinberg, Mark A ; Reich, Kristian ; Morris, Alun ; Papp, Kim A

BACKGROUNDSonelokimab (also known as M1095) is a novel trivalent nanobody comprised of monovalent camelid-derived (ie, from the Camelidae family of mammals, such as camels, llamas, and alpacas) nanobodies specific to human interleukin (IL)-17A, IL-17F, and human serum albumin. Nanobodies are a novel class of proprietary therapeutic proteins based on single-domain, camelid, heavy-chain-only antibodies. We assessed the efficacy, safety, and tolerability of sonelokimab across four dosage regimens compared with placebo in patients with plaque-type psoriasis. Secukinumab served as an active control.METHODSThis multicentre, randomised, placebo-controlled, phase 2b trial was done at 41 clinics and research sites in Bulgaria, Canada, Czech Republic, Germany, Hungary, Poland, and the USA. Participants (aged 18-75 years) with stable moderate to severe plaque-type psoriasis (defined as an Investigator's Global Assessment [IGA] score of ≥3, a body surface area involvement of ≥10%, and a Psoriasis Area and Severity Index score of ≥12) for more than 6 months before randomisation, who were candidates for systemic biological therapy were included. Participants previously treated with more than two biologics or any therapy targeting IL-17 were excluded. Randomisation was stratified by weight (≤90 kg or >90 kg) and previous use of biologics. Investigators, participants, and vendors remained masked for the duration of the study, with the exception of each site's study drug administrator (who did not complete any other assessments in the study) and a study monitor who only assessed drug preparation, administration, and accountability. The study sponsor remained masked until all week 24 data were clean and locked. Participants were randomly assigned (1:1:1:1:1:1) using a centralised interactive response technology system to one of six parallel treatment groups: placebo group, sonelokimab 30 mg group, sonelokimab 60 mg group, sonelokimab 120 mg normal load group, sonelokimab 120 mg augmented load group, or secukinumab 300 mg group. All participants underwent a 4-week screening period, a 12-week placebo-controlled induction period, a 12-week dose maintenance or escalation period, and a 24-week response assessment or dose-holding period. During the placebo-controlled induction period (weeks 0-12), participants received either placebo (at weeks 0, 1, 2, 3, 4, 6, 8, and 10), sonelokimab 30 mg, 60 mg, or 120 mg normal load (at weeks 0, 2, 4, and 8), sonelokimab 120 mg augmented load (at weeks 0, 2, 4, 6, 8, and 10), or secukinumab 300 mg (at weeks 0, 1, 2, 3, 4, and 8), with placebo given at weeks 1, 3, 6, and 10 in the sonelokimab 30 mg, 60 mg, and 120 mg normal load groups, at weeks 1 and 3 in the sonelokimab 120 mg augmented load group, and at weeks 6 and 10 in the secukinumab 300 mg group. During the dose maintenance or escalation period (weeks 12-24), participants assigned to the placebo group received sonelokimab 120 mg (at weeks 12, 14, 16, and then every 4 weeks); those assigned to sonelokimab 30 mg or 60 mg groups with an IGA score of more than 1 were escalated to 120 mg and then every 4 weeks, and those with an IGA score of 1 or less stayed on the assigned dose at week 12 and then every 4 weeks; those assigned to the sonelokimab 120 mg groups received sonelokimab 120 mg at week 12 and then every 8 weeks (normal load group) or every 4 weeks (augmented load); and those assigned to the secukinumab 300 mg group received secukinumab 300 mg at week 12 and then every 4 weeks. During this period, placebo was given at week 14 in all groups, except in participants who initially received placebo, and at week 16 in the sonelokimab 120 mg normal load group. In the response assessment with dose-holding period (weeks 24-48), participants in the sonelokimab 30 mg or 60 mg groups who had dose escalation to 120 mg remained on the same regimen regardless of the IGA score at week 24. Participants in the secukinumab 300 mg group also remained on the same regimen regardless of IGA score at week 24. Participants in the sonelokimab 30 mg and 60 mg groups without dose escalation, and all participants in the two sonelokimab 120 mg groups (including placebo rollover patients) were eligible to stop the study drug at week 24. Those participants with an IGA score of 0 at week 24 received placebo; these participants resumed the previous dose of sonelokimab every 4 weeks when they had an IGA score of 1 or more (assessed every 4 weeks). Participants in these groups with an IGA score of 1 or more at week 24 continued on the same dosage. All study treatments were administered as subcutaneous injections. The final dose in all groups was given at week 44. The primary outcome was the proportion of participants in the sonelokimab groups with an IGA of clear or almost clear (score 0 or 1) at week 12 compared with the placebo group. The primary outcome and safety outcomes were assessed on an intention-to-treat basis. The study was not powered for formal comparisons between sonelokimab and secukinumab groups. This trial is registered with ClinicalTrials.gov, NCT03384745.FINDINGSBetween Aug 15, 2018, and March 27, 2019, 383 patients were assessed for eligibility, 313 of whom were enrolled and randomly assigned to the placebo group (n=52), the sonelokimab 30 mg group (n=52), the sonelokimab 60 mg group (n=52), the sonelokimab 120 mg normal load group (n=53), the sonelokimab 120 mg augmented load group (n=51), or the secukinumab 300 mg group (n=53). Baseline characteristics of participants were similar among the groups. At week 12, none (0·0% [95% CI 0·0-6·8]) of the 52 participants in the placebo group had an IGA score of 0 or 1 versus 25 (48·1% [34·0-62·4], p<0·0001) of 52 participants in the sonelokimab 30 mg group, 44 (84·6% [71·9-93·1], p<0·0001) of 52 participants in the sonelokimab 60 mg group, 41 (77·4% [63·8-87·7], p<0·0001) of 53 participants in the sonelokimab 120 mg normal load group, 45 (88·2% [76·1-95·6], p<0·0001) of 51 participants in the sonelokimab 120 mg augmented load group, and 41 (77·4% [63·8-87·7], p<0·0001) of 53 participants in the secukinumab 300 mg group. During the placebo-controlled induction period, 155 (49·5%) of 313 participants had one or more mostly mild to moderate adverse event; the most frequent adverse events in all participants on sonelokimab during weeks 0-12 were nasopharyngitis (28 [13·5%] of 208 participants), pruritus (14 [6·7%] participants), and upper respiratory tract infection (nine [4·3%] participants). One patient from all sonelokimab-containing groups had Crohn's disease that developed during weeks 12-52. Over 52 weeks, sonelokimab safety was similar to secukinumab, with the possible exception of manageable Candida infections (one [1·9%] of 53 participants in the secukinumab group had a Candida infection vs 19 [7·4%] of 257 participants in all sonelokimab-containing groups).INTERPRETATIONTreatment with sonelokimab doses of 120 mg or less showed significant clinical benefit over placebo, with rapid onset of treatment effect, durable improvements, and an acceptable safety profile.FUNDINGAvillion.

2013-11-01·Journal of Periodontology2区 · 医学

Gingival Crevicular Fluid, Serum Levels of Receptor Activator of Nuclear Factor‐κB Ligand, Osteoprotegerin, and Interleukin‐17 in Patients With Rheumatoid Arthritis and Osteoporosis and With Periodontal Disease

2区 · 医学

Article

作者: David Lappin ; Pınar Gümüş ; Christopher Nile ; Eralp Buduneli ; Başak Bıyıkoğlu ; Kenan Aksu ; Fulden Saraç ; Nurcan Buduneli

Background: This study is performed to evaluate gingival crevicular fluid (GCF) and serum levels of soluble receptor activator of nuclear factor‐κB ligand (sRANKL), interleukin (IL)‐17A, IL‐17E, IL‐17F, IL‐17A/F, and osteoprotegerin (OPG) in women with rheumatoid arthritis (RA), osteoporosis (OPR), and those who are systemically healthy (SH), all with periodontal disease.Methods: GCF and serum samples were obtained before any periodontal intervention from 17 women with RA, 19 with OPR, and 13 who were SH with periodontitis. Full‐mouth clinical periodontal measurements were recorded. sRANKL, OPG, and IL‐17 levels were determined by enzyme‐linked immunosorbent assay.Results: Clinical periodontal measurements were similar in the three study groups. Although the total amounts of GCF albumin, OPG, IL‐17A, and IL‐17A/F were similar in the study groups, there were statistically significant differences in GCF concentrations of sRANKL, OPG, IL‐17A, IL‐17E, IL‐17F, and IL‐17A/F. The sRANKL/OPG ratios were significantly higher in the RA group than in the OPR and SH groups (P <0.05). Serum sRANKL, sRANKL/OPG, and IL‐17A/IL‐17E ratios were significantly higher, whereas OPG concentrations were significantly lower in the RA group compared to other groups (P <0.05). Serum IL‐17A concentrations were significantly higher in the RA and OPR groups than in the SH group (P <0.05).Conclusion: Increased inflammatory mediator levels in patients with RA, despite the long‐term use of various anti‐inflammatory drugs, suggest that these patients may have a propensity to overproduce these inflammatory mediators.

Biomedicines

Metabolic Dysfunction-Associated Steatotic Liver Disease: The Associations between Inflammatory Markers, TLR4, and Cytokines IL-17A/F, and Their Connections to the Degree of Steatosis and the Risk of Fibrosis

Article

作者: Hangan, Adriana Corina ; Orășan, Olga Hilda ; Filip, Gabriela Adriana ; Negrean, Vasile ; Sitar-Tăut, Adela-Viviana ; Coste, Sorina-Cezara ; Procopciuc, Lucia Maria ; Lucaciu, Roxana Liana ; Iancu, Mihaela ; Cozma, Angela

Background: The pathogenesis of MASLD (metabolic dysfunction-associated steatotic liver disease) is driven by environmental, genetic, metabolic, immune, and inflammatory factors. IL-17 and TLR4 determine hepatic steatosis, inflammation, and finally fibrosis. Objectives: To explore the associations between the plasma levels of inflammatory markers, TLR4, and the cytokines IL17A/F, as well as their connections with the degree of hepatic steatosis and the risk of hepatic fibrosis (defined by the FIB-4 score) in MASLD patients. Methods: The study cohort included 80 patients diagnosed with MASLD. The IL-17A/F and TLR4 serum concentrations were determined using the ELISA method. Results: We found a significant difference in the CAR levels (C-reactive protein to albumin ratio) when comparing MASLD patients with severe steatosis to those with mild/moderate steatosis (Student’s t test, t (71) = 2.32, p = 0.023). The PIV (pan-immune inflammatory value) was positively correlated with the SII (systemic immune inflammation index), (r = 0.86, p < 0.0001) and the CAR (r = 0.41, p = 0.033) in MASLD patients with severe steatosis. In contrast, increased values of the LMR (lymphocyte to monocyte ratio) were significantly associated, with decreased levels of the SII (ρ = −0.38, p = 0.045). We also found a positive correlation between the CAR and the SII (r = 0.41, p = 0.028). In patients with mild/moderate steatosis, a significant positive correlation was observed between the SII and IL17A (r = 0.36, p = 0.010), the PIV and the CAR (r = 0.29, p = 0.011), the PIV and the SII (r = 0.87, p < 0.0001) and the PIV and IL17A (r = 0.3, p = 0.036). A negative correlation was observed between the LMR and the SII (r = −0.55, p < 0.0001) and the CAR and IL17F (r = −0.37, p = 0.011). Regarding the inflammatory markers, the PIV (336.4 vs. 228.63, p = 0.0107), and the SII (438.47 vs. 585.39, p = 0.0238) had significantly lower levels in patients with an intermediate–high risk of hepatic fibrosis as compared with the patients with a low risk of hepatic fibrosis. The PNI (prognostic nutritional index) (47.16 vs. 42.41, p = 0.0392) had significantly different levels in patients with the likelihood of hepatic fibrosis than those with a low risk of hepatic fibrosis. Conclusions: Regarding the inflammatory markers, the PIV and the SII hold promise as biomarkers for discriminating between MASLD patients with an intermediate–high risk and those with a low risk of hepatic fibrosis. Our findings underscore the role of IL-17A and its potential relationship with inflammatory markers in MASLD pathogenesis and the progression to hepatic fibrosis.

项与 IL-17A x albumin x IL-17F 相关的新闻（医药）

2024-02-29

·GlobeNewswire-Health Care

MoonLake Immunotherapeutics Reports Full Year 2023 Financial Results, Recent Business Highlights and Announces an R&D Day on March 10

MoonLake Immunotherapeutics Reports Full Year 2023 Financial Results, Recent Business Highlights and Announces an R&D Day on March 10 A successful year including the announcements of positive data from two Phase 2 trials of sonelokimab in hidradenitis suppurativa (HS), at 12 and 24 weeks, and active psoriatic arthritis (PsA), at 12 weeks, supporting a potential best-in-class profile across two key indications Phase 3 preparation for sonelokimab in HS nearing completion, following positive feedback from both FDA and EMAYear-end cash, cash equivalents and short-term marketable debt securities of $511.0 million, expected to support a roadmap rich in potential catalysts whilst providing a cash runway to the end of 2026R&D Day to be held on Sunday March 10 – alongside the American Academy of Dermatology (AAD) annual meeting – expected to include 24 week data from the ARGO PsA study and PsA program next steps, final plans for the HS Phase 3 VELA program, analysis of the size of the HS market, as well as catalyst updates including new pipeline indications ZUG, Switzerland, February 29, 2024 – MoonLake Immunotherapeutics (NASDAQ: MLTX) (“MoonLake”), a clinical-stage biotechnology company focused on creating next-level therapies for inflammatory diseases, today announced its financial results for the fourth quarter and year ended December 31, 2023, and provided recent business highlights. Dr. Jorge Santos da Silva, Chief Executive Officer of MoonLake Immunotherapeutics, said: “2023 was another momentous year for MoonLake in the inflammation and immunology field. We reported positive results from two global Phase 2 trials of our Nanobody® sonelokimab in hidradenitis suppurativa (HS) and active psoriatic arthritis. We were highly selective in our choice of endpoints for these trials in a deliberate plan to raise the bar for patients suffering from these diseases characterized by profound patient burden and significant unmet medical need. Following highly encouraging interactions with both the FDA and EMA regarding our data and forthcoming Phase 3 trial designs for HS, we are completing plans to initiate our Phase 3 trials for both indications. On top of this, support from world-renowned experts, clinicians, and patient organizations for our data, science and methodologies continues to mount. We look forward to sharing more information with everyone at our upcoming R&D Day on 10 March.” Q4 highlights (including post-quarter end) Announced landmark top-line 12-week data from the global Phase 2 ARGO clinical trial of sonelokimab in patients with PsA in November, supporting a potential best-in-class profileAnnounced positive full 24-week data from the global Phase 2 MIRA clinical trial in October, achieving the primary endpoint, HiSCR75, with sonelokimab in patients with HS, in support of a highly promising and differentiated therapeutic solutionAnnounced positive feedback from both FDA and EMA on the regulatory path for the Phase 3 VELA program of sonelokimab in HS, with the Phase 3 trial having a similar design to the validated Phase 2 trial and being in line with MoonLake’s prior communications and expectations Fourth quarter and year-end financial results As of December 31, 2023, MoonLake held cash, cash equivalents and short-term marketable debt securities of $511.0 million, compared to $496.0 million as of September 30, 2023. The increase of $15.0 million was primarily attributable to the gross proceeds of at-the-market offerings, partially offset by cash used in the Company’s operations. Matthias Bodenstedt, Chief Financial Officer at MoonLake Immunotherapeutics, said: “MoonLake has added considerable shareholder value over the past year, and we are driven to continue building on this. In December of last year, and in early 2024, we pursued at-the-market offerings, bringing in gross proceeds of $85 million at minimal dilution. The new funds allow us to double down on the clinical development of sonelokimab across multiple indications, whilst securing an additional expected cash runway to the end of 2026. We are looking forward to sharing updates on our roadmap rich in potential catalysts, together with the highly anticipated 24 week data from our ARGO study in active psoriatic arthritis, at our upcoming R&D Day.” Research and development expenses for the fourth quarter ended December 31, 2023 were $8.1 million, compared to $7.6 million in the previous quarter. Research and development expenses for the year ended December 31, 2023 were $31.8 million, compared to $42.0 million in the previous year. The decrease was primarily driven by a decrease in milestone expense incurred under the in-licensing agreement of sonelokimab. General and administrative expenses for the fourth quarter ended December 31, 2023 were $6.9 million, compared to $5.4 million in the previous quarter. General and administrative expenses for the year ended December 31, 2023 were $22.3 million which was similar to the $23.0 million incurred in the prior year. Other non-operating income increased from $0.6 million in the prior year to $10.1 million for the year ended December 31, 2023. The increase was primarily attributable to interest income achieved from investments in short-term marketable debt securities. Net loss for the year ended December 31, 2023 was $44.1 million, compared to $64.5 million for the prior year ending December 31, 2022. R&D Day, on Sunday, March 10 MoonLake will be hosting an R&D Day for investors and analysts in San Diego, USA on Sunday, March 10 alongside the American Academy of Dermatology (AAD) annual meeting. The event will take place from 09:00 – 11:30 PST/ 12:00 – 14:30 EST/18:00 – 20:30 CET at the Hotel Westin Bayview, San Diego and will be webcast for virtual attendees. The R&D Day will provide important business updates from MoonLake’s executive team including: Outcome of the end-of-Phase 2 (EoP2) interactions with the FDA and EMA, and plans for the Phase 3 VELA program for the Nanobody® sonelokimab in HS, expected to randomize the first patient in Q2 2024Analysis of the HS and PsA market opportunities and leadership potential for sonelokimab24-week data from the ARGO trial in active PsA, plans related to EoP2 FDA meeting in Q2 2024 and expectation to randomize the first patient in Q4 2024Pipeline updates and details on the additional catalysts for 2024 and 2025, including new indications to be pursuedFinancials The event will feature presentations from leading clinicians in dermatology and rheumatology. Professor Joesph F. Merola, Founding President of the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network Consortium (PPACMAN) and Vice President of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis), and Professor Kenneth B. Gordon, Chair of Dermatology at the Medical College of Wisconsin, will share their perspectives on the potential of MoonLake’s investigational Nanobody® sonelokimab in IL-17A and IL-17F driven inflammatory diseases. A live Q&A session involving all presenters will follow the event. Register to attend either the in-person event or webcast here. A recording and additional details will be available on the Events & Presentations section of the Company’s website at www.ir.moonlaketx.com. Upcoming banking conferences Leerink Partners Global Biopharma Conference: March 11-13 (Miami)Jefferies Biotech on the Bay Summit: March 11-13 (Miami)Barclays 26th Annual Global Healthcare Conference: March 12-14 (Miami)H.C. Wainwright 2nd Annual Autoimmune & Inflammatory Disease Virtual Conference, March 28 (virtual)23rd Annual Needham Virtual Healthcare Conference: April 8-11 (virtual)Van Lanschot Kempen Life Sciences Conference Amsterdam: April 16-17 (Amsterdam) - Ends - About MoonLake Immunotherapeutics MoonLake Immunotherapeutics is a clinical-stage biopharmaceutical company unlocking the potential of sonelokimab, a novel investigational Nanobody® for the treatment of inflammatory disease, to revolutionize outcomes for patients. Sonelokimab inhibits IL-17A and IL-17F by inhibiting the IL-17A/A, IL-17A/F, and IL-17F/F dimers that drive inflammation. The company’s focus is on inflammatory diseases with a major unmet need, including hidradenitis suppurativa and psoriatic arthritis – conditions affecting millions of people worldwide with a large need for improved treatment options. MoonLake was founded in 2021 and is headquartered in Zug, Switzerland. Further information is available at www.moonlaketx.com. About Nanobodies® Nanobodies® represent a new generation of antibody-derived targeted therapies. They consist of one or more domains based on the small antigen-binding variable regions of heavy-chain-only antibodies (VHH). Nanobodies® have a number of potential advantages over traditional antibodies, including their small size, enhanced tissue penetration, resistance to temperature changes, ease of manufacturing, and their ability to be designed into multivalent therapeutic molecules with bespoke target combinations.The terms Nanobody® and Nanobodies® are trademarks of Ablynx, a Sanofi company. About Sonelokimab Sonelokimab (M1095) is an investigational ~40 kDa humanized Nanobody® consisting of three VHH domains covalently linked by flexible glycine-serine spacers. With two domains, sonelokimab selectively binds with high affinity to IL-17A and IL-17F, thereby inhibiting the IL-17A/A, IL-17A/F, and IL-17F/F dimers. A third central domain binds human albumin, facilitating further enrichment of sonelokimab at sites of inflammatory edema. Sonelokimab is being assessed in two trials, the Phase 2 ARGO trial in PsA and the Phase 2 MIRA trial in HS. In June 2023, topline results of the MIRA trial (NCT05322473) at 12 weeks showed that the trial met its primary endpoint, the Hidradenitis Suppurativa Clinical Response (HiSCR)75, which is a higher measure of clinical response versus the HiSCR50 measure used in other clinical trials, setting a landmark milestone. In October 2023, the full dataset from the MIRA trial at 24 weeks showed that maintenance treatment with sonelokimab led to further improvements in HiSCR75 response rates and other clinically relevant outcomes. In November 2023, MoonLake announced positive top-line results from its global Phase 2 ARGO trial evaluating the efficacy and safety of the Nanobody® sonelokimab in patients with active psoriatic arthritis (PsA). The trial met its primary endpoint with a statistically significant greater proportion of patients treated with either sonelokimab 60mg or 120mg (with induction) achieving an American College of Rheumatology (ACR)50 response compared to those on placebo at week 12. All key secondary endpoints in the trial were met for the 60mg and 120mg doses with induction. Sonelokimab has also been assessed in a randomized, placebo-controlled Phase 2b trial (NCT03384745) in 313 patients with moderate-to-severe plaque-type psoriasis. High threshold clinical responses (Investigator’s Global Assessment Score 0 or 1, and Psoriasis Area and Severity Index 90/100) were observed in patients with moderate-to-severe plaque-type psoriasis. Sonelokimab was generally well tolerated, with a safety profile similar to the active control, secukinumab (Papp KA, et al. Lancet. 2021; 397:1564-1575). In an earlier Phase 1 trial in patients with moderate-to-severe plaque-type psoriasis, sonelokimab has been shown to decrease (to normal skin levels) the cutaneous gene expression of pro-inflammatory cytokines and chemokines (Svecova D. J Am Acad Dermatol. 2019;81:196-203). Sonelokimab is not yet approved for use in any indication. Sonelokimab is not yet approved for use in any indication. About the MIRA trialThe MIRA trial (M1095-HS-201) is a global, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the Nanobody® sonelokimab, administered subcutaneously, in the treatment of adult patients with active moderate-to-severe hidradenitis suppurativa. The trial recruited 234 patients, with the aim to evaluate two different doses of sonelokimab (120mg and 240mg) with placebo control and adalimumab as an active reference arm. The primary endpoint of the trial is the percentage of participants achieving Hidradenitis Suppurativa Clinical Response 75 (HiSCR75), defined as a ≥75% reduction in total abscess and inflammatory nodule (AN) count with no increase in abscess or draining tunnel count relative to baseline. The trial also evaluated a number of secondary endpoints, including the proportion of patients achieving HiSCR50, the change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4), the proportion of patients achieving a Dermatology Life Quality Index (DLQI) total score of ≤5, and the proportion of patients achieving at least 30% reduction from baseline in Numerical Rating Scale (NRS30) in the Patient’s Global Assessment of Skin Pain (PGA Skin Pain). Further details are available at: https://www.clinicaltrials.gov/ct2/show/NCT05322473 About the ARGO trialThe ARGO trial (M1095-PSA-201) is a global, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the Nanobody® sonelokimab, administered subcutaneously, in the treatment of adult patients with active PsA. The trial is designed to evaluate different doses of sonelokimab, with placebo control and adalimumab as an active reference arm. The primary endpoint of the trial is the percentage of participants achieving ≥50% improvement in signs and symptoms of disease from baseline, compared to placebo, as measured by the American College of Rheumatology (ACR) 50 response. The trial also evaluates a number of secondary endpoints, including improvement compared to placebo in ACR20, complete skin clearance as measured by at least a 100% improvement in the Psoriasis Area and Severity Index (PASI), physical function as measured by the Health Assessment Questionnaire-Disability Index, enthesitis as measured by the Leeds Enthesitis Index and pain as measured by the Patients Assessment of Arthritis Pain. Further details are available at: https://clinicaltrials.gov/ct2/show/NCT05640245 Cautionary Statement Regarding Forward Looking StatementsThis press release contains certain “forward-looking statements” within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements include, but are not limited to, statements regarding MoonLake’s expectations, hopes, beliefs, intentions or strategies regarding the future including, without limitation, statements regarding: plans for and timing of clinical trials, including expectations regarding the timing of the Phase 3 programs in HS and PsA, the efficacy and safety of sonelokimab for the treatment of HS and PsA, including in comparison to existing standards or care or other competing therapies, clinical trials and research and development programs and the anticipated timing of the results from those studies and trials, the initiation of work in and the timing of future announcements regarding additional indications for sonelokimab, the timing for meeting with regulatory authorities, expectations regarding future catalysts, and our anticipated cash usage and the period of time we anticipate such cash to be available. In addition, any statements that refer to projections, forecasts, or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “would” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that statement is not forward looking. Forward-looking statements are based on current expectations and assumptions that, while considered reasonable by MoonLake and its management, as the case may be, are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with MoonLake’s business in general and limited operating history; expectations regarding the timing of the Phase 3 programs in HS and PsA; positive results from a clinical trial may not necessarily be predictive of the results of future or ongoing clinical studies; MoonLake’s substantial dependence on the success of its Nanobody® sonelokimab; state and federal healthcare reform measures that could result in reduced demand for MoonLake’s product candidates and reliance on third parties to conduct and support its and clinical trials. Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. MoonLake does not undertake or accept any duty to release publicly any updates or revisions to any forward-looking statements to reflect any change in its expectations or in the events, conditions or circumstances on which any such statement is based. CONTACT: MoonLake Immunotherapeutics Investors Matthias Bodenstedt, CFO ir@moonlaketx.com MoonLake Immunotherapeutics Media Patricia Sousa, Director Corporate Affairs media@moonlaketx.com ICR ConsiliumMary-Jane Elliott, Ashley Tapp, Namrata Taak Tel: +44 (0) 20 3709 5700MoonLake@consilium-comms.com MOONLAKE IMMUNOTHERAPEUTICS CONSOLIDATED BALANCE SHEETS (Amounts in USD, except share data) December 31, 2023 September 30, 2023 (Unaudited)Current assets Cash and cash equivalents $ 451,169,337 $ 318,165,809Short-term marketable debt securities 59,838,900 177,812,899Other receivables 1,056,862 720,755Prepaid expenses - current 2,102,203 3,310,281Total current assets 514,167,302 500,009,744 Non-current assets Operating lease right-of-use assets 3,628,480 169,422Property and equipment, net 320,865 39,520Prepaid expenses - non-current 8,423,468 —Total non-current assets 12,372,813 208,942Total assets $ 526,540,115 $ 500,218,686 Current liabilities Trade and other payables $ 1,837,684 $ 3,404,728 Short-term portion of operating lease liabilities 1,197,876 156,338Accrued expenses and other current liabilities 6,930,120 6,746,951Total current liabilities 9,965,680 10,308,017 Non-current liabilities Long-term portion of operating lease liabilities 2,499,990 13,084Pension liability 583,426 255,399Total non-current liabilities 3,083,416 268,483Total liabilities 13,049,096 10,576,500Commitments and contingencies Equity (deficit) Class A Ordinary Shares: $0.0001 par value; 500,000,000 shares authorized; 60,466,453 shares issued and outstanding as of December 31, 2023; 53,561,488 shares issued and outstanding as of September 30, 2023 6,047 5,356Class C Ordinary Shares: $0.0001 par value; 100,000,000 shares authorized; 2,505,476 shares issued and outstanding as of December 31, 2023; 8,884,517 shares issued and outstanding as of September 30, 2023 251 889Additional paid-in capital 609,969,236 531,271,953Accumulated deficit (116,657,472) (109,220,396)Accumulated other comprehensive income 2,357,621 2,875,198Total shareholders’ equity (deficit) 495,675,683 424,933,000Noncontrolling interests 17,815,336 64,709,186Total equity 513,491,019 489,642,186Total liabilities and equity $ 526,540,115 $ 500,218,686 MOONLAKE IMMUNOTHERAPEUTICS CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (Amounts in USD, except share and per share data) For the Three Months Period Ended For the Year Ended December 31, September 30, December 31, December 31, 2023 2023 2023 2022Operating expenses Research and development $ (8,097,794) $ (7,585,136) $ (31,801,880) $ (42,048,954)General and administrative (6,931,096) (5,391,607) (22,321,216) (23,012,463)Total operating expenses (15,028,890) (12,976,743) (54,123,096) (65,061,417)Operating loss (15,028,890) (12,976,743) (54,123,096) (65,061,417) Other income, net 7,185,810 1,386,313 10,138,367 591,732Loss before income tax (7,843,080) (11,590,430) (43,984,729) (64,469,685) Income tax expense (44,309) (28,923) (94,388) (36,366)Net loss $ (7,887,389) $ (11,619,353) $ (44,079,117) $ (64,506,051)Of which: net loss attributable to controlling interests shareholders (7,437,074) (9,426,049) (36,007,260) (49,973,249)Of which: net loss attributable to noncontrolling interests shareholders (450,315) (2,193,304) (8,071,857) (14,532,802) Net unrealized gain on marketable securities and short-term investments (716,437) 3,437,291 2,330,101 390,753Actuarial income (loss) on employee benefit plans (317,256) 39,157 (336,579) 269,893Other comprehensive income (1,033,693) 3,476,448 1,993,522 660,646Comprehensive loss $ (8,921,082) $ (8,142,905) $ (42,085,595) $ (63,845,405)Comprehensive loss attributable to controlling interests shareholders (8,415,796) (6,590,259) (34,511,723) (49,437,461)Comprehensive loss attributable to noncontrolling interests (505,286) (1,552,646) (7,573,872) (14,407,944) Weighted-average number of Class A Ordinary Shares, basic and diluted 59,914,592 53,517,655 49,122,534 29,361,353Basic and diluted net loss per share attributable to controlling interests shareholders $ (0.12) $ (0.18) $ (0.73) $ (1.70) Attachment 20240229 MoonLake Q4 and RD Day FINAL

临床结果临床2期临床1期临床3期财报

2023-10-11

·BioSpace

MoonLake Immunotherapeutics presents positive 12-week data from the Phase 2 MIRA trial with Nanobody® Sonelokimab for Hidradenitis Suppurativa at the European Academy of Dermatology and Venereology Congress Peer reviewed data presented during a late-breaking session at the European Academy of Dermatology and Venereology Congress (EADV) confirms the strong pro sonelokimab in HS announced at MLTX’s R&D Day on June 26, 2023 HiSCR75 primary endpoint met with a significantly higher proportion of patients on sonelokimab 120mg (43.3%) compared to placebo (14.7%) achieving HiSCR75 at week 12; a 29 percentage points (ppt) delta (p<0.001) HiSCR50 secondary endpoint met with a significantly higher proportion of patients on sonelokimab 120mg (65.7%) compared to placebo (27.9%) achieving HiSCR50 at week 12; a 38 ppt delta (p<0.001) Sonelokimab rapidly achieved high levels of response across HiSCR thresholds, including HiSCR 90 and IHS4, and significant resolution of draining tunnels (DT 100) compared to placebo Sonelokimab also led to significant improvements in patient-reported quality of life, skin pain, and HS symptoms compared with placebo, with additional depth of response reported following additional analysis after the June R&D Day Safety results of sonelokimab were consistent with previously reported studies with no new observed signals, and included additional insight following further analysis after the June R&D Day 24-week data from the Phase 2 MIRA trial is anticipated imminently ZUG, Switzerland, October 11, 2023 – MoonLake Immunotherapeutics (“MoonLake”; Nasdaq: MLTX), a clinical-stage biotechnology company focused on creating next-level therapies for inflammatory diseases, announced that positive 12-week results from its global Phase 2 MIRA trial evaluating the efficacy and safety of the Nanobody® sonelokimab in patients with moderate-to-severe hidradenitis suppurativa (“HS”) were presented today during a late-breaking session at the European Academy of Dermatology and Venereology Congress (“EADV”) held in Berlin, Germany. The EADV presentation follows the announcement, in June 2023, of the positive topline 12-week results from the trial in 234 patients, which marked a landmark milestone as the first placebo-controlled randomized trial in HS to report results using HiSCR75 as the primary endpoint. The primary analysis was based on the most stringent type of analysis for such trials, intent-to-treat non-responder imputation (“ITT-NRI”). The MIRA trial met its primary endpoint with a significantly higher proportion of patients treated with both sonelokimab 120mg (43.3%) and 240mg (34.8%) achieving HiSCR75 compared to those on placebo (14.7%) at week 12. Sonelokimab also met the key secondary endpoint with a significantly higher proportion of patients treated with both sonelokimab 120mg (65.7%) and 240mg (53.0%) achieving HiSCR50 compared to those on placebo (27.9%) at week 12. Both doses performed similarly, with the 120mg dose providing the highest delta on HiSCR75 and HiSCR50. The 120mg dose achieved a 29 percentage points (ppt) delta to placebo on HiSCR75 (p<0.001) and a 38 ppt delta to placebo on HiSCR50 (p<0.01). As early as week 8, a significant difference in response between sonelokimab and placebo was observed across HiSCR thresholds, including HiSCR90. In addition, other clinically relevant secondary endpoints also reached statistical significance at week 12 with sonelokimab compared with placebo. This included improvements in International Hidradenitis Suppurativa Severity Score System (“IHS") 4, significantly greater complete resolution of draining tunnels (DT 100) as well as significant improvements in patient reported quality of life, skin pain, and HS symptoms. The safety pro sonelokimab was consistent with previously reported studies with no new safety signals observed. Overall, sonelokimab continues to show a favorable safety profile, in line with the known pro IL-17 inhibitors. Professor Brian Kirby MD, FRCPI, Charles Department of Dermatology, St. Vincent’s University Hospital and Charles Institute of Dermatology, University College Dublin, Dublin, Ireland, commented: “Hidradenitis suppurativa is a severely debilitating chronic skin condition resulting in irreversible tissue destruction and scarring. Patients often suffer great pain and become socially isolated. There is an urgent need for effective new treatments to help patients manage their disease. The positive 12-week data presented at EADV today with sonelokimab are highly encouraging and I look forward to seeing further data and the start of the Phase III clinical program.” Kristian Reich, MD, PhD, Founder and Chief Scientific Officer at MoonLake, added: “We observed maximum clinical responses of our Nanobody® sonelokimab at the lower 120mg dose tested, demonstrating the advantage of using a smaller biologic with albumin-binding capacity to inhibit IL-17A and IL-17F. We now look forward to reporting the 24-week data imminently which will provide important insights on the depth and breadth of efficacy of sonelokimab and further data on safety.” Full results from the MIRA trial will be submitted for publication in a peer-reviewed medical journal and for presentation at an upcoming scientific meeting. Sonelokimab has already been successfully assessed in a randomized, placebo-controlled, Phase 2b trial (NCT03384745) in 313 patients with moderate-to-severe plaque-type psoriasis in which it demonstrated a rapid and durable skin clearance (PASI100) with no unexpected safety findings. Sonelokimab is currently being evaluated in a Phase 2 trial (NCT05640245), ‘ARGO’, in patients with active psoriatic arthritis. The top-line 12-week results are expected in the first half of November 2023, ahead of the American College of Rheumatology Conference, November 10-15. Sonelokimab is not yet approved for use in any indication. - Ends – About Hidradenitis Suppurativa Hidradenitis suppurativa is a severely debilitating chronic skin condition resulting in irreversible tissue destruction. HS manifests as painful inflammatory skin lesions, typically around the armpits, groin, and buttocks. Over time, uncontrolled and inadequately treated inflammation can result in irreversible tissue destruction and scarring. The disease affects 0.05–4.1% of the global population, with three times more females affected than males. Onset typically occurs in early adulthood and HS has a profound negative impact on quality of life, with a higher morbidity than other dermatologic conditions. There is increasing scientific evidence to support IL-17A- and IL-17F-mediated inflammation as a key driver of the pathogenesis of HS, with other identified risk factors including genetics, cigarette smoking, and obesity. About the MIRA trial The MIRA trial (M1095-HS-201) is a global, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the Nanobody® sonelokimab, administered subcutaneously, in the treatment of adult patients with active moderate-to-severe hidradenitis suppurativa. The trial recruited 234 patients, with the aim to evaluate two different doses of sonelokimab (120mg and 240mg) with placebo control and adalimumab as an active reference arm. The primary endpoint of the trial is the percentage of participants achieving Hidradenitis Suppurativa Clinical Response 75 (HiSCR75), defined as a ≥75% reduction in total abscess and inflammatory nodule (AN) count with no increase in abscess or draining tunnel count relative to baseline. The trial also evaluated a number of secondary endpoints, including the proportion of patients achieving HiSCR50, the change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4), the proportion of patients achieving a Dermatology Life Quality Index (DLQI) total score of ≤5, and the proportion of patients achieving at least 30% reduction from baseline in Numerical Rating Scale (NRS30) in the Patient’s Global Assessment of Skin Pain (PGA Skin Pain). Further details are available at: . About Sonelokimab Sonelokimab (M1095) is an investigational ~40 kDa humanized Nanobody® consisting of three VHH domains covalently linked by flexible glycine-serine spacers. With two domains, sonelokimab selectively binds with high affinity to IL-17A and IL-17F, thereby inhibiting the IL-17A/A, IL-17A/F, and IL-17F/F dimers. A third central domain binds to human albumin, facilitating further enrichment of sonelokimab at sites of inflammatory edema. Sonelokimab is currently being assessed in two ongoing trials, the Phase 2 MIRA trial in HS and the Phase 2 ARGO trial in PsA. The MIRA trial met its primary endpoint, the Hidradenitis Suppurativa Clinical Response (HiSCR) 75 which is a higher measure of clinical response versus the HiSCR50 measure used in other clinical trials. A significantly greater proportion of patients treated with both sonelokimab 120mg and 240mg achieved HiSCR75 compared to those on placebo at week 12. The positive results suggest that, as early as week 12, sonelokimab, relative to placebo, reaches the highest clinical activity among all other therapies tested in similarly stringent pivotal-like trials. The trial proceeds to week 24, with a 4-week safety follow-up. Sonelokimab has been assessed in a randomized, placebo-controlled Phase 2b study in 313 patients with moderate-to-severe plaque-type psoriasis. Sonelokimab demonstrated a rapid and durable clinical response (Investigator’s Global Assessment Score 0 or 1, Psoriasis Area and Severity Index 90/100) in patients with moderate-to-severe plaque-type psoriasis. Sonelokimab was generally well tolerated, with a safety pro to the active control, secukinumab (Papp KA, et al. Lancet. 2021; 397:1564-1575). In an earlier Phase 1 study in patients with moderate-to-severe plaque-type psoriasis, sonelokimab has been shown to decrease (to normal skin levels) the cutaneous gene expression of pro-inflammatory cytokines and chemokines (Svecova D. J Am Acad Dermatol. 2019;81:196–203). Currently, a global phase 2 trial in psoriatic arthritis (NCT05640245, M1095-PSA-201, “ARGO”) including multiple arms and over 200 patients is ongoing (announced on Dec 14, 2022). About Nanobodies® Nanobodies® represent a new generation of antibody-derived targeted therapies. They consist of one or more domains based on the small antigen-binding variable regions of heavy-chain-only antibodies (VHH). Nanobodies® have a number of potential advantages over traditional antibodies, including their small size, enhanced tissue penetration, resistance to temperature changes, ease of manufacturing, and their ability to be designed into multivalent therapeutic molecules with bespoke target combinations. The terms Nanobody® and Nanobodies® are trademarks of Ablynx, a Sanofi company. About MoonLake Immunotherapeutics MoonLake Immunotherapeutics is a clinical-stage biopharmaceutical company unlocking the potential of sonelokimab, a novel investigational Nanobody® for the treatment of inflammatory disease, to revolutionize outcomes for patients. Sonelokimab inhibits IL-17A and IL-17F by inhibiting the IL-17A/A, IL-17A/F, and IL-17F/F dimers that drive inflammation. The company’s focus is on inflammatory diseases with a major unmet need, including hidradenitis suppurativa and psoriatic arthritis – conditions affecting millions of people worldwide with a large need for improved treatment options. MoonLake was founded in 2021 and is headquartered in Zug, Switzerland. Further information is available at . Cautionary Statement Regarding Forward Looking Statements This press release contains certain “forward-looking statements” within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements include, but are not limited to, statements regarding MoonLake’s expectations, hopes, beliefs, intentions or strategies regarding the future including, without limitation, statements regarding: plans for clinical trials and research and development programs; and the anticipated timing of the results from those trials, including completing the MIRA trial and the ARGO trial; and the efficacy of our products, if approved, including in relation to other products. In addition, any statements that refer to projections, forecasts, or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “would” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that such statement is not forward looking. Forward-looking statements are based on current expectations and assumptions that, while considered reasonable by MoonLake and its management, as the case may be, are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with MoonLake’s business in general and limited operating history, difficulty enrolling patients in clinical trials, and reliance on third parties to conduct and support its clinical trials, and the other risks described in or incorporated by reference into MoonLake’s Annual Report on Form 10-K for the year ended December 31, 2022 and subsequent filings with the Securities and Exchange Commission. Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. MoonLake does not undertake or accept any duty to release publicly any updates or revisions to any forward-looking statements to reflect any change in its expectations or in the events, conditions or circumstances on which any such statement is based. MoonLake Immunotherapeutics Investors Matthias Bodenstedt, CFO info@moonlaketx.com MoonLake Immunotherapeutics Media Patricia Sousa media@moonlaketx.com ICR Consilium Mary-Jane Elliott, Namrata Taak, Ashley Tapp Tel: +44 (0) 20 3709 5700 media@moonlaketx.com MoonLake@consilium-comms.com

临床结果临床2期临床3期

2023-06-29

·药研网

IL-17战场，谁主沉浮

从2009年至2019年，免疫疾病药物在全球药品销售额Top100中的占比由8%提升至27%，市场突破千亿美元，成为仅次于肿瘤的第二大市场。据医药魔方数据库数据，国外已上市自身免疫领域创新疗法为377款，国内为117款。2022年全球自身免疫疾病药物市场规模约1317亿美元，而中国自身免疫疾病药物市场规模约36亿美元。但是根据卫健委统计显示，中国自身免疫性疾病发病人数约8000万人，无论是国内还是国外，自免疫疾病治疗还有巨大需尚未被满足，随之热门靶点IL-17的竞争也开始变得激烈。IL-17由Th17细胞特异性分泌。该家族包括6 个成员的配体(IL-17A~IL-17F)和5个受体(IL-17RA~IL-17RD和SEF)。IL-17A和IL-17F可以以同源二聚体或IL-17A/IL-17F异源二聚体的形式由免疫细胞分泌,通过L17RA和IL-17RC亚基组成的受体二聚体传递刺激信号。DOI: 10.1007/978-3-030-38315-2在IL-17靶向药市场，针对IL-17A、IL-17RA和IL-17A/F的赛道比较火热。目前全球已有5款药物获批上市，FDA和中国批准了3款，分别是Brodalumab，Ixekizumab和Secukinumab。诺华的司库奇尤单抗作为首个获批上市的IL-17药物，已经拿下了多个适应症，2022年销额47.88亿美元，排在首位，目前还在持续扩展适应症，已获批适应症覆盖强直性脊柱炎、银屑病、化脓性汗腺炎、银屑病关节炎等。礼来的依奇珠单抗也不甘示弱，针对脊柱炎和银屑病两个领域获批了多项适应症，2022年销额24.82亿美元。而首款IL-17RA拮抗剂 Brodalumab因为自杀意念和行为的黑框警告，销量有所影响，这也促进了司库奇尤和依奇珠单抗销量的增长。照此趋势，IL-17市场有望突破百亿美元。与此同时，多款创新药物持续发力，试图抢占市场。USB的Bimekizumab于2021年欧盟获批，2022年销额为3500万欧元，对比之下，司库奇尤单抗和依奇珠单抗的先发优势还是很明显的，同时BKZ已在美国和中国申报上市，其销量还有增长的空间。BKZ是首个治疗中重度斑块状银屑病的 IL-17 A/F 双重抑制剂，机制与司库奇尤单抗和依奇珠单抗有所不同，且给药频率更低，后期只需每8周一次。3项III期临床研究（BKZ分别与乌司奴单抗、安慰剂和阿达木单抗比较）显示，第 16 周时，BKZ的皮肤清除率水平具有统计学显著优效性（PASI改善≥ 90%）。与司库奇尤单抗头对头中，PASI 100 的皮肤清除率在统计学上具有显著优效性。今年刚发布的长效研究中，BKZ可维持疗效长达104周，也就是两年多，此外，从阿达木单抗转换至BKZ能迅速改善患者的治疗应答。https://doi.org/10.1093/bjd/ljac021和BKZ具有相似机制的纳米三抗Sonelokimab（SLK）也备受关注，相继在银屑病和化脓性汗腺炎（HS）的II期获得成功，被给予厚望，这款药的拥有者MoonLake从上市以来股价一路上涨，近一年上涨了891%。SLK主要特点是分子量小，只有约40KDa。近期刚公布的2期结果中，主要终点12周HiSCR 75较安慰剂高29%。单从该数据来看SLK有望成为BIC，MoonLake股价也应声大涨，但MoonLake此次对比的是BKZ的两项3期数据 BE HEARD I/II。回看BKZ的2期数据，HiSCR75较安慰剂高出了39%。doi: 10.1001/jamadermatol.2021.2905但从患者规模来看，BKZ的2期入组90人，两项3期入组超500人，SLK的2期入组234人，所以SLK的2期数据要比BKZ的2期数据更可靠一些，但具体疗效还需等待3期以及与阿达木单抗的对比结果。此外，SLK的成功让另一款小分子量药物Lzokibep也受到了关注，靶向IL-17A和血清白蛋白，分子量仅18.6kDa，对IL-17A的表观亲和力是典型抗体的1000倍。国外百花齐放，国内也在紧紧追赶。创响生物拿到了lzokibep的大中华权益，而智翔金泰和恒瑞医药在今年3月和4月相继申报上市。Vunakizumab为 IgG1抗IL-17A单抗，已在成人中重度慢性斑块型银屑病、成人强直性脊柱炎III期临床研究中证实可缓解疾病进展且安全性耐受性良好。图源：医药魔方；恒瑞医药此外，康方生物、三生国建和丽珠生物已经进展到3期，君实、再鼎、先声、百奥泰等都在布局，其中先声药业从药物类型上走差异化，开发的是口服小分子总结：从当前情况来看，在研药物基本上都是选择与阿达木单抗或司库奇尤单抗头对头，但从目前结果来看，已经出现了比其疗效更优，给药频次更低的药物，且当前所有管线的在研适应症非常相似，还会面临其他靶点的竞争，此外，阿达木单抗和司库奇尤单抗有先发优势，后来者要居上会比较困难。细胞系产品查询投稿丨商务合作加入交流群往期推荐中生制药企业梳理PD1+ADC开卷：信达与荣昌达成合作2023 H1 国产创新药license-out盘点点击下方“药研网”，关注更多精彩内容

上市批准免疫疗法临床3期