A Phase II Trial to Evaluate the Safety and Efficacy of clazakizumab for the desensitisation of highly sensitized patients on the deceased donor kidney transplant waiting list

Start Date06 May 2024

Sponsor / Collaborator

Royal Melbourne Hospital

NCT05727384 / RecruitingPhase 2IIT

Reducing Inflammation for Greater Health Trial: the RIGHT Study

The goal of this clinical trial is to learn about the effects of inflammation-lowering therapy on mobility and disability in older adults. The main questions it aims to answer are:
* Will therapy improve walking speed/pace?
* Will therapy improve levels of blood inflammation markers and other indicators of physical, cognitive and immune function?
Participants will be asked to receive injections of drug or placebo every 4 weeks for 24 weeks. They will also be asked to undergo testing that assesses physical function, thinking ability and brain health, breathing capacity, and blood vessel stiffness, and will have blood samples collected to measure immune function and to create a bank of samples for future testing. Comparisons will be made between those who receive drug and those who receive placebo.

Start Date01 Aug 2023

Sponsor / Collaborator

University of Pittsburgh

[+1]

NCT05485961 / RecruitingPhase 2/3

A Phase 2b/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Combined Dose-Finding and Cardiovascular Outcome Study to Investigate the Efficacy and Safety of CSL300 (Clazakizumab) in Subjects With End Stage Kidney Disease Undergoing Dialysis

This is a 2-part (phase 2b/3) prospective, interventional, multicenter, randomized, double blind, placebo controlled study. Part 1 (phase 2b) is a dose-finding study for CSL300 vs placebo. Part 2 (phase 3) aims to assess the efficacy of CSL300 on CV outcomes and safety in subjects with ASCVD or diabetes mellitus and evidence of systemic inflammation who are undergoing maintenance dialysis.

Start Date21 Oct 2022

Sponsor / Collaborator

CSL Behring LLC

100 Clinical Results associated with Clazakizumab

100 Translational Medicine associated with Clazakizumab

100 Patents (Medical) associated with Clazakizumab

Literatures (Medical) associated with Clazakizumab

01 Aug 2024·NATURE MEDICINE

IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial

Article

Author: Tricoci, Pierluigi ; Velkoska, Elena ; Zoccali, Carmine ; Heise, Mark ; Mehran, Roxana ; Wheeler, David C ; Chang, Anna Marie ; Lokhnygina, Yuliya ; Jardine, Meg ; Clementi, Regina ; Ridker, Paul M ; Felker, G Michael ; Gibson, C Michael ; Stenvinkel, Peter ; Mahaffey, Kenneth W ; Charytan, David M ; Wang, Angela Yee-Moon ; Levin, Adeera ; Goodman, Shaun G ; Wolf, Myles ; Fellström, Bengt ; Mears, Jenny ; Chertow, Glenn M

Abstract:

Inflammation mediated by interleukin-6 (IL-6) is strongly associated with cardiovascular risk. Here we evaluated clazakizumab, a monoclonal antibody targeting the IL-6 ligand, in a phase 2b dose-finding study. Adults with cardiovascular disease and/or diabetes receiving maintenance dialysis with high-sensitivity C-reactive protein (hs-CRP) ≥ 2 mg l−1 at baseline were randomized to receive clazakizumab (2.5 mg, 5 mg or 10 mg, n = 32 per dose group) or placebo (n = 31) every 4 weeks. The primary endpoint was the change from baseline in hs-CRP to week 12, expressed as the geometric mean ratio. Clazakizumab treatment signficantly reduced serum hs-CRP concentrations at week 12 by 86%, 90% and 92% relative to placebo in patients randomized to 2.5 mg, 5 mg or 10 mg clazakizumab, respectively (all P < 0.0001), meeting the primary outcome. With regard to secondary endpoints, clazakizumab treatment reduced serum fibrinogen, amyloid A, secretory phospholipase A2, and lipoprotein(a) concentrations, as well as increased mean serum albumin concentrations at 12 weeks, relative to placebo. The proportion of patients who achieved hs-CRP < 2.0 mg l−1 was 79%, 82% and 79% in the 2.5 mg, 5 mg and 10 mg clazakizumab groups, respectively, compared with 0% of placebo-treated patients. With regard to safety, no cases of sustained grade 3 or 4 thrombocytopenia or neutropenia were observed. Serious infections were seen with similar frequency in the placebo, clazakizumab 2.5 mg and clazakizumab 5 mg groups, but were numerically more frequent in the clazakizumab 10 mg group. The results of this trial indicate that in patients receiving maintenance dialysis, clazakizumab reduced inflammatory biomarkers associated with cardiovascular events. ClinicalTrials.gov registration: NCT05485961.

01 Aug 2024·Kidney360

New Therapies for Highly Sensitized Patients on the Waiting List

Review

Author: Jordan, Stanley C ; Vo, Ashley ; Ammerman, Noriko

Exposure to HLA alloantigens through pregnancy, blood products, and previous transplantations induce powerful immunologic responses that create an immunologic barrier to successful transplantation. This is commonly detected through screening for HLA antibodies using Luminex beads coated with HLA antigens at transplant evaluation. Currently accepted approaches to desensitization include plasmapheresis/low-dose or high-dose intravenous Ig plus anti-CD20. However, these approaches are often unsuccessful because of the inability to remove high titer circulating HLA antibodies and limit rebound responses by long-lived anti-HLA antibody secreting plasma cells (PCs) and memory B cells (BMEM). This is especially significant for patients with a calculated panel reactive antibody of 99%–100%. Newer desensitization approaches, such as imlifidase (IgG endopeptidase), rapidly inactivate IgG molecules and create an antibody-free zone by cleaving IgG into F(ab’2) and Fc fragments, thus eliminating complement and cell-mediated injury to the graft. This represents an important advancement in desensitization. However, the efficacy of imlifidase is limited by pathogenic antibody rebound, increasing the potential for antibody-mediated rejection. Controlling antibody rebound requires new strategies that address the issues of antibody depletion and inhibition of BMEM and PC responses. This will likely require a combination of agents that effectively and rapidly deplete pathogenic antibodies and prevent immune cell activation pathways responsible for antibody rebound. Here, using anti–IL-6 receptor (tocilizumab) or anti–IL-6 (clazakizumab) could offer long-term control of BMEM and PC donor-specific HLA antibody responses. Agents aimed at eliminating long-lived PCs (anti-CD38 and anti–B-cell maturation antigen×CD3) are likely to benefit highly HLA sensitized patients. Complement inhibitors and novel agents aimed at inhibiting Fc neonatal receptor IgG recycling will be important in desensitization. Administering these agents alone or in combination will advance our ability to effectively desensitize patients and maintain durable suppression post-transplant. After many years of limited options, advanced therapeutics will likely improve efficacy of desensitization and improve access to kidney transplantation for highly HLA sensitized patients.

01 Aug 2024·NATURE MEDICINE

Author Correction: IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial

Author: Tricoci, Pierluigi ; Velkoska, Elena ; Zoccali, Carmine ; Heise, Mark ; Wheeler, David C ; Mehran, Roxana ; Chang, Anna Marie ; Lokhnygina, Yuliya ; Clementi, Regina ; Jardine, Meg ; Ridker, Paul M ; Felker, G Michael ; Gibson, C Michael ; Mahaffey, Kenneth W ; Stenvinkel, Peter ; Charytan, David M ; Wang, Angela Yee-Moon ; Levin, Adeera ; Goodman, Shaun G ; Wolf, Myles ; Fellström, Bengt ; Chertow, Glenn M ; Mears, Jenny

News (Medical) associated with Clazakizumab

14 Aug 2024

·www.globenewswire.com

VYNE Therapeutics Reports Second Quarter 2024 Financial Results and Provides Business Update

Initiated Phase 2b trial of VYN201 in nonsegmental vitiligo, with top-line results expected in mid-2025Phase 1a SAD/MAD trial of VYN202 progressing, with data from the SAD and MAD portions expected in Q3 and Q4 2024, respectivelyBalance sheet expected to fund key clinical milestones for VYN201 and VYN202 through the end of 2025 BRIDGEWATER, N.J., Aug. 14, 2024 (GLOBE NEWSWIRE) -- VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a clinical-stage biopharmaceutical company focused on developing differentiated therapies to treat chronic inflammatory and immune-mediated conditions with high unmet need, today announced financial results as of and for the three and six months ended June 30, 2024 and provided a business update. "We advanced our clinical programs in the second quarter of 2024, highlighted by the initiation of our Phase 2b trial of VYN201 and the Phase 1a trial of VYN202," said David Domzalski, President and Chief Executive Officer of VYNE. "We are pleased with the progress we are making with both clinical programs. We remain on track to report top-line data from our Phase 2b clinical trial for VYN201 in subjects with nonsegmental vitiligo in the middle of next year. We also expect to report top-line data from the single ascending dose portion of the Phase 1a trial of VYN202 this quarter, followed by results from the multiple ascending dose portion in the fourth quarter. Upon the successful completion of this Phase 1a trial, we plan to advance VYN202 into two Phase 1b proof-of-concept trials with top-line readouts in the second half of next year." Recent Pipeline Updates VYN201 VYN201 is a locally administered pan-bromodomain ("BD") BET inhibitor designed as a “soft” drug to address diseases involving multiple, diverse inflammatory cell signaling pathways while providing low systemic exposure. VYNE initiated a Phase 2b trial of VYN201 in nonsegmental vitiligo in June 2024. The Phase 2b trial is a randomized, double-blind, vehicle-controlled trial evaluating the efficacy, safety and pharmacokinetics of once-daily VYN201 gel in three dose cohorts (1%, 2% and 3% concentrations) compared to vehicle for 24 weeks. Subjects are being randomized at 1:1:1:1 ratio. Following the 24-week treatment period, subjects in the 1%, 2%, and 3% cohorts will continue treatment with their respective dose concentrations for an additional 28-week open label extension. Subjects in the vehicle group during the initial 24-week treatment period will be equally re-randomized to receive VYN201 1%, 2% or 3% gel for an additional 28 weeks. VYNE expects to enroll approximately 40 subjects in each arm and to report top-line results from the 24-week double-blind portion of the trial in mid-2025. VYN202 VYN202 is an oral small molecule BD2-selective BET inhibitor designed to achieve potential class-leading selectivity and potency (BD2 vs. BD1). A first-in-human Phase 1a single ascending dose/multiple ascending dose ("SAD/MAD") trial was initiated in June 2024. VYNE expects to report top-line results from the SAD and MAD portions of the trial in the third and fourth quarters of 2024, respectively. If the Phase 1a trial is successfully completed, VYNE plans to initiate Phase 1b trials in adult subjects with moderate-to-severe plaque psoriasis and moderate-to-severe rheumatoid arthritis, with top-line results anticipated in the second half of 2025. Recent Corporate Update In July, VYNE appointed Subhashis Banerjee, M.D., as Senior Vice President of Clinical Development. Dr. Banerjee is a trained immunologist and rheumatologist with over 25 years of drug development experience at large pharmaceutical companies, including the development of therapies for psoriasis and arthritic conditions. He most recently served as Vice President & Disease Area Head, Rheumatology and Dermatology at Bristol Myers Squibb. Dr. Banerjee played a key role in the development strategy of immunology assets across multiple platforms for several immune-mediated diseases, including SOTYKTU® (deucravacitinib), ORENCIA® (abatacept), clazakizumab (anti-IL-6 antibody), TALTZ® (ixekizumab, anti-IL-17 antibody) and XELJANZ® (tofacitinib). Upcoming Conference Participation H.C. Wainwright 26th Annual Global Investment Conference, September 9-11, 2024, New York, NYStifel Immunology and Inflammation Virtual Summit, September 17-18, 2024 Financial Results as of and for the Second Quarter Ended June 30, 2024 Cash position. As of June 30, 2024, VYNE had cash, cash equivalents, restricted cash and marketable securities of $78.1 million. VYNE believes its cash, cash equivalents, restricted cash and marketable securities as of June 30, 2024 will be sufficient to fund its operations through the end of 2025. Revenues. Revenues totaled $0.2 million and $0.1 million for each of the quarters ended June 30, 2024 and 2023, respectively, consisting of royalty revenue from the Company's royalty agreement with LEO Pharma, to whom VYNE previously licensed the rights to Finacea® foam. Research and development expenses. VYNE’s research and development expenses for the quarter ended June 30, 2024 were $7.3 million, representing an increase of $0.1 million, or 1.0%, compared to $7.2 million for the quarter ended June 30, 2023. The increase was primarily driven by expenses related to preparatory and clinical trial activities for a Phase 2b trial of VYN201 in subjects with nonsegmental vitiligo, which was initiated in June 2024, of $3.2 million, including a $1.0 million development milestone payment due to Tay Therapeutics Ltd. ("Tay") upon the initiation of the Phase 2b trial. In addition, employee-related expenses increased by $0.3 million following the hiring of additional research and development personnel. These increases were partially offset by a decrease in expenses associated with VYN202 of $3.5 million, primarily driven by lower amounts owed to Tay under the license agreement with respect to VYN202 (the "VYN202 License Agreement"). In April 2023, VYNE made a one-time cash payment of $3.75 million to Tay in connection with entering into the VYN202 License Agreement. In the second quarter of 2024, the Company incurred a $1.0 million development milestone payment due to Tay following the initiation of a Phase 1a SAD/MAD trial of VYN202. General and administrative expenses. VYNE’s general and administrative expenses for the quarter ended June 30, 2024 were $3.3 million, representing an increase of $0.1 million, or 2.1%, compared to $3.2 million for the quarter ended June 30, 2023. The increase was primarily driven by consulting and professional fees. Net loss. Net loss and net loss per share for the quarter ended June 30, 2024 were $9.4 million and $0.22, respectively, compared to a net loss and net loss per share of $10.1 million and $3.09, respectively for the comparable period in 2023. About VYNE Therapeutics Inc. VYNE is a clinical-stage biopharmaceutical company focused on developing differentiated therapies to treat chronic inflammatory and immune-mediated conditions with high unmet need. VYNE's unique and proprietary BET inhibitors, which comprise its InhiBET™ platform, are designed to overcome limitations of early generation BET inhibitors by leveraging alternative routes of administration and enhanced selectivity. For more information about VYNE Therapeutics Inc. or its product candidates, visit www.vynetherapeutics.com. VYNE may use its website to comply with its disclosure obligations under Regulation FD. Therefore, investors should monitor VYNE’s website in addition to following its press releases, filings with the U.S. Securities and Exchange Commission, public conference calls, and webcasts. Investor Relations:John FrauncesLifeSci Advisors, LLC917-355-2395jfraunces@lifesciadvisors.com Tyler ZerondaVYNE Therapeutics Inc.908-458-9106Tyler.Zeronda@VYNEtx.com Media Relations: Mike BeyerSam Brown Inc.312-961-2502mikebeyer@sambrown.com Cautionary Statement Regarding Forward-Looking StatementsThis release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding VYNE's ability to successfully complete its Phase 1a trial of VYN202, future clinical trials of VYN202, the expected enrollment and timing for reporting top-line results from trials of VYN201 and VYN202, VYNE’s projected cash runway, and other statements regarding the future expectations, plans and prospects of VYNE. All statements in this press release which are not historical facts are forward-looking statements. Any forward-looking statements are based on VYNE’s current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties and assumptions that could cause actual results to differ materially and adversely from those set forth or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: VYNE’s ability to successfully develop its product candidates; the timing of commencement of future preclinical studies and clinical trials; VYNE’s ability to complete and receive favorable results from clinical trials of its product candidates; VYNE’s ability to obtain additional funding, either through equity or debt financing transactions or collaboration arrangements; and VYNE’s ability to comply with various regulations applicable to its business. For a discussion of other risks and uncertainties, and other important factors, any of which could cause VYNE’s actual results to differ from those contained in the forward-looking statements, see the section titled “Risk Factors” in VYNE’s Annual Report on Form 10-K for the year ended December 31, 2023, and VYNE’s other filings from time to time with the U.S. Securities and Exchange Commission. Although VYNE believes these forward-looking statements are reasonable, they speak only as of the date of this announcement and VYNE undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law. Given these risks and uncertainties, you should not rely upon forward-looking statements as predictions of future events. Third-party products and company names mentioned herein may be the trademarks of their respective owners. VYNE THERAPEUTICS INC.CONDENSED CONSOLIDATED BALANCE SHEETS(U.S. dollars in thousands, except share and per share data)(Unaudited) June 30, December 31, 2024 2023 Assets Current Assets: Cash and cash equivalents$29,609 $30,620 Restricted cash 46 54 Investment in marketable securities 48,492 62,633 Prepaid and other current assets 5,629 2,656 Total Current Assets 83,776 95,963 Non-current Assets: Operating lease right-of-use assets 151 207 Non-current prepaid expenses and other assets 2,721 1,515 Total Non-current Assets 2,872 1,722 Total Assets$86,648 $97,685 Liabilities and Stockholders’ Equity Current Liabilities: Trade payables$4,516 $1,659 Accrued expenses 5,069 4,119 Employee related obligations 736 1,645 Operating lease liabilities 120 115 Other current liabilities 1,313 — Total Current Liabilities 11,754 7,538 Long-term Liabilities: Non-current operating lease liabilities 25 99 Other liabilities — 1,313 Total Long-term Liabilities 25 1,412 Total Liabilities 11,779 8,950 Commitments and Contingencies Stockholders' Equity: Preferred stock: $0.0001 par value; 20,000,000 shares authorized at June 30, 2024 and December 31, 2023; no shares issued and outstanding at June 30, 2024 and December 31, 2023 — — Common stock: $0.0001 par value; 150,000,000 shares authorized at June 30, 2024 and December 31, 2023; 14,536,124 and 14,098,888 shares issued and outstanding at June 30, 2024 and December 31, 2023, respectively 1 1 Additional paid-in capital 781,917 780,044 Accumulated other comprehensive (loss) income (58) 26 Accumulated deficit (706,991) (691,336)Total Stockholders' Equity 74,869 88,735 Total Liabilities and Stockholders’ Equity$86,648 $97,685 VYNE THERAPEUTICS INC.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(U.S. dollars in thousands, except per share data)(Unaudited) Three Months EndedJune 30, Six Months EndedJune 30, 2024 2023 2024 2023 Revenues Royalty revenues$198 $135 $296 $234 Total Revenues 198 135 296 234 Operating Expenses: Research and development 7,306 7,233 11,014 9,967 General and administrative 3,288 3,220 7,058 6,460 Total Operating Expenses 10,594 10,453 18,072 16,427 Operating Loss (10,396) (10,318) (17,776) (16,193)Other income, net 1,001 280 2,140 543 Loss from continuing operations before income taxes (9,395) (10,038) (15,636) (15,650)Income tax expense — — — — Loss from continuing operations (9,395) $(10,038) (15,636) (15,650)Loss from discontinued operations, net of income taxes (11) (20) (19) (30)Net Loss$(9,406) $(10,058) $(15,655) $(15,680) Loss per share from continuing operations, basic and diluted$(0.22) $(3.08) $(0.37) $(4.81)Income (loss) per share from discontinued operations, basic and diluted$0.00 $(0.01) $0.00 $(0.01)Loss per share, basic and diluted$(0.22) $(3.09) $(0.37) $(4.82) Weighted average shares outstanding - basic and diluted 42,586 3,274 42,584 3,265

Phase 1Phase 2Financial StatementExecutive ChangeLicense out/in

02 Nov 2022

·www.prnewswire.com

Next-Generation mRNA, Gene Therapy, Plasma Products, Monoclonal Antibodies, and Recent Acquisitions and Collaborations Highlight CSL R&D Day 2022

Pipeline advancements and investment in innovation and disruptive technologies to help fuel sustainable, profitable growth for CSL's three businesses, CSL Behring, CSL Seqirus and CSL Vifor, in the decades ahead MELBOURNE, Australia and KING OF PRUSSIA, Pa., Nov. 2, 2022 /PRNewswire/ -- At its annual R&D investor briefing today, global biotechnology leader CSL (ASX:CSL; USOTC:CSLLY) demonstrated how its growing, innovative pipeline is well-positioned to meet the current and future needs of patients and public health. CSL revealed progress and plans in advancing assets that have the potential to disrupt current standards of care in its areas of focus (immunology, haematology, respiratory, cardiovascular and metabolic, transplant, nephrology, vaccines) using its strategic scientific platforms (plasma protein technology, recombinant technology, cell and gene therapy, and sa-mRNA, adjuvanted, cell-based and egg-based vaccines). Among the highlights presented were the following: Late-Stage Development Includes Disruptive Innovation and New Additions to the CSL Portfolio Etranacogene dezaparvovec (also known as CSL222), an investigational gene therapy for the treatment of adults with haemophilia B has been accepted for priority review by the United States (US) Food and Drug Administration (FDA) and standard review by the European Medicines Agency (EMA). If approved, etranacogene dezaparvovec would be the first-ever gene therapy treatment option for the haemophilia B community. The regulatory filings are supported by results from the pivotal HOPE-B trial, the largest gene therapy trial in haemophilia B to date. The multi-year clinical development program for etranacogene dezaparvovec was led by uniQure (Nasdaq: QURE) and sponsorship of the clinical trials has transitioned to CSL after acquiring global rights to commercialize the investigational treatment. Top-line Phase III results for garadacimab (CSL312, anti-FXIIa), an investigational first-in-class monoclonal antibody being developed as a long-term preventive treatment for patients with hereditary angioedema, demonstrated that the study met its primary and secondary efficacy objectives and showed favourable safety and tolerability. CSL aims to begin filing for approval with global regulatory authorities next calendar year. Garadacimab was discovered and optimised by scientists at CSL's Bio21–based Research site, with formulation and manufacturing for the clinical programs completed at the CSL Broadmeadows Biotech Manufacturing Facility. CSL Vifor brings a leading portfolio of therapies in nephrology, dialysis and iron deficiency. New late-stage assets to the pipeline include Sparsentan for IgA nephropathy and focal segmental glomerulosclerosis (FSGS) and SNF472 for calciphylaxis and calcific uremic arteriolopathy (CUA). R&D Portfolio Progress Across Areas of Focus and Scientific Platforms Clazakizumab, an anti-IL6 monoclonal antibody, intended for the treatment of chronic active antibody-mediated rejection (AMR) in kidney transplant recipients continues to progress in the Phase III IMAGINE trial. This is CSL's leading program for clazakizumab, which will also be investigated in a Phase IIb/III study for improvement of cardiovascular (CV) outcomes in dialysis patients. CSL plans to engage Fresenius Medical Care dialysis centres in the study. AEGIS-II, a Phase III, multicenter, double-blind, randomised, placebo-controlled, parallel-group study to evaluate the efficacy and safety of CSL112, compared to placebo, in reducing the risk of major adverse CV events (MACE) in patients following a heart attack, will enrol the last patient by the end of 2022, with completion of the trial expected towards the end of 2023. CSL is advancing the Phase IIb study for its adjuvanted, cell-based high-dose quadrivalent influenza vaccine (aQIVc). This study will help CSL further build the body of clinical evidence to support the optimal formulation for when the company moves into the Phase III immunogenicity and safety study for aQIVc. Published results from the preclinical studies of CSL's self-amplifying messenger RNA (sa-mRNA) influenza vaccine candidates, the next generation of mRNA vaccines, indicate a potent, cross-reactive immune response against pandemic and seasonal influenza strains, A(H5N1) and A(H1N1). CSL's sa-mRNA candidate is expected to enter clinical trials in 2023. Recently Announced Collaboration and license agreement with Arcturus Therapeutics aims to accelerate next-generation mRNA capabilities in influenza, pandemic preparedness and other selected respiratory viral pathogens -- including a near term COVID-19 vaccine that has recently reported interim results from a large Phase III efficacy study, meeting its primary and secondary endpoints of prevention of infection and severe disease with a favourable safety profile. A strategic option and license agreement with Translational Sciences to license TS23, a first-in-class anti-α2-antiplasmin monoclonal antibody. TS23 is being developed to dissolve thrombi that cause serious conditions such as pulmonary embolism (PE) and acute ischemic stroke (AIS). The treatment candidate is soon to be evaluated in the US in the NAIL-IT Phase II study, which has been designed to evaluate the safety and thrombolytic effect of ascending doses of TS23 in patients with sub-massive (intermediate risk) PE. "CSL is on the leading-edge of innovation in areas we know well and we have strategically and methodically built a pipeline that has never been more robust with diverse sources of innovation, from in-house and external sources, that include the disruptive scientific platforms of gene therapy and sa-mRNA," said Dr. Bill Mezzanotte, Executive Vice President, Head of R&D, and Chief Medical Officer for CSL. "Our enhanced capabilities across all of our scientific platforms and therapeutic focus areas will help us in our relentless pursuit to deliver on our promise to help patients lead full lives, protect public health and sustainably grow our business in the decades ahead, while providing promising futures for our employees." In fiscal year 2021-2022, CSL invested approximately $1.16 billion in R&D. This includes growing CSL R&D's footprint in Melbourne, Australia; Marburg, Germany; throughout Switzerland and Waltham, Massachusetts – helping to create an integrated global organization that can conveniently collaborate with institutions everywhere -- offering scientists a wide array of opportunities for professional development and enhancing access to external innovation. Advancing External Innovation: The Biotechnology Incubator at CSL's Global Headquarters in Melbourne, Australia Names Its Operator CSL, WEHI and The University of Melbourne have appointed Cicada Innovations as the independent operator of the new biotech incubator which will be located in CSL's new global headquarters currently under construction in the Melbourne Biomedical Precinct. The appointment follows the project partners joining forces to create an incubator for biotech start-up companies, with the Victorian Government's landmark Breakthrough Victoria Fund providing funding to support the AU$95 million project. It will be Australia's first and only incubator that is co-located with a leading biopharmaceutical company and will have space for up to 40 start-ups. "Incubator residents will be working in an innovation-driven environment alongside a large and focused CSL R&D team, enabling opportunities for peer-collaboration, learning and sharing of ideas," said Dr. Andrew Nash, CSL's Chief Scientific Officer and Senior Vice President, Research. "The strong collaboration between CSL, the University of Melbourne, WEHI, Breakthrough Victoria and now Cicada Innovations has been critical to bring the incubator to fruition and reflects CSL's values and desire to deliver on our promise to patients worldwide." For more about the incubator, . For more on CSL's R&D Investor Briefing, please visit . About CSL CSL Limited (ASX: CSL; USOTC: CSLLY) is a leading global biotechnology company with a dynamic portfolio of lifesaving medicines, including those that treat haemophilia and immune deficiencies, as well as vaccines to prevent influenza. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL – including our three businesses, CSL Behring, CSL Seqirus, and CSL Vifor – provides lifesaving products to patients in more than 100 countries and employs more than 30,000 people. Our unique combination of commercial strength, R&D focus, and operational excellence enables us to identify, develop and deliver innovations so our patients can live life to the fullest. For inspiring stories about the promise of biotechnology, visit CSLBehring.com/Vita and follow us on Twitter.com/CSL. For more information visit . Media Contacts: Greg Healy Email: [email protected] +1 610 906 4564 In Australia: Jimmy Baker Email: [email protected] +61 450 909 211 Kim O'Donohue Email: [email protected] +61 449 884 603 In Europe: Jasmin Joller Email: [email protected] SOURCE CSL

VaccineCollaborateGene TherapyAntibodyFinancial Statement

02 Nov 2022

·www.biospace.com

Next-Generation mRNA, Gene Therapy, Plasma Products, Monoclonal Antibodies, and Recent Acquisitions and Collaborations Highlight CSL R&D Day 2022

Pipeline advancements and investment in innovation and disruptive technologies to help fuel sustainable, profitable growth for CSL's three businesses, CSL Behring, CSL Seqirus and CSL Vifor, in the decades ahead MELBOURNE, Australia and KING OF PRUSSIA, Pa., Nov. 2, 2022 /PRNewswire/ -- At its annual R&D investor briefing today, global biotechnology leader CSL (ASX:CSL; USOTC:CSLLY) demonstrated how its growing, innovative pipeline is well-positioned to meet the current and future needs of patients and public health. CSL revealed progress and plans in advancing assets that have the potential to disrupt current standards of care in its areas of focus (immunology, haematology, respiratory, cardiovascular and metabolic, transplant, nephrology, vaccines) using its strategic scientific platforms (plasma protein technology, recombinant technology, cell and gene therapy, and sa-mRNA, adjuvanted, cell-based and egg-based vaccines). Among the highlights presented were the following: Late-Stage Development Includes Disruptive Innovation and New Additions to the CSL Portfolio Etranacogene dezaparvovec (also known as CSL222), an investigational gene therapy for the treatment of adults with haemophilia B has been accepted for priority review by the United States (US) Food and Drug Administration (FDA) and standard review by the European Medicines Agency (EMA). If approved, etranacogene dezaparvovec would be the first-ever gene therapy treatment option for the haemophilia B community. The regulatory filings are supported by results from the pivotal HOPE-B trial, the largest gene therapy trial in haemophilia B to date. The multi-year clinical development program for etranacogene dezaparvovec was led by uniQure (Nasdaq: QURE) and sponsorship of the clinical trials has transitioned to CSL after acquiring global rights to commercialize the investigational treatment. Top-line Phase III results for garadacimab (CSL312, anti-FXIIa), an investigational first-in-class monoclonal antibody being developed as a long-term preventive treatment for patients with hereditary angioedema, demonstrated that the study met its primary and secondary efficacy objectives and showed favourable safety and tolerability. CSL aims to begin filing for approval with global regulatory authorities next calendar year. Garadacimab was discovered and optimised by scientists at CSL's Bio21–based Research site, with formulation and manufacturing for the clinical programs completed at the CSL Broadmeadows Biotech Manufacturing Facility. CSL Vifor brings a leading portfolio of therapies in nephrology, dialysis and iron deficiency. New late-stage assets to the pipeline include Sparsentan for IgA nephropathy and focal segmental glomerulosclerosis (FSGS) and SNF472 for calciphylaxis and calcific uremic arteriolopathy (CUA). R&D Portfolio Progress Across Areas of Focus and Scientific Platforms Clazakizumab, an anti-IL6 monoclonal antibody, intended for the treatment of chronic active antibody-mediated rejection (AMR) in kidney transplant recipients continues to progress in the Phase III IMAGINE trial. This is CSL's leading program for clazakizumab, which will also be investigated in a Phase IIb/III study for improvement of cardiovascular (CV) outcomes in dialysis patients. CSL plans to engage Fresenius Medical Care dialysis centres in the study. AEGIS-II, a Phase III, multicenter, double-blind, randomised, placebo-controlled, parallel-group study to evaluate the efficacy and safety of CSL112, compared to placebo, in reducing the risk of major adverse CV events (MACE) in patients following a heart attack, will enrol the last patient by the end of 2022, with completion of the trial expected towards the end of 2023. CSL is advancing the Phase IIb study for its adjuvanted, cell-based high-dose quadrivalent influenza vaccine (aQIVc). This study will help CSL further build the body of clinical evidence to support the optimal formulation for when the company moves into the Phase III immunogenicity and safety study for aQIVc. Published results from the preclinical studies of CSL's self-amplifying messenger RNA (sa-mRNA) influenza vaccine candidates, the next generation of mRNA vaccines, indicate a potent, cross-reactive immune response against pandemic and seasonal influenza strains, A(H5N1) and A(H1N1). CSL's sa-mRNA candidate is expected to enter clinical trials in 2023. Recently Announced Collaboration and license agreement with Arcturus Therapeutics aims to accelerate next-generation mRNA capabilities in influenza, pandemic preparedness and other selected respiratory viral pathogens -- including a near term COVID-19 vaccine that has recently reported interim results from a large Phase III efficacy study, meeting its primary and secondary endpoints of prevention of infection and severe disease with a favourable safety profile. A strategic option and license agreement with Translational Sciences to license TS23, a first-in-class anti-α2-antiplasmin monoclonal antibody. TS23 is being developed to dissolve thrombi that cause serious conditions such as pulmonary embolism (PE) and acute ischemic stroke (AIS). The treatment candidate is soon to be evaluated in the US in the NAIL-IT Phase II study, which has been designed to evaluate the safety and thrombolytic effect of ascending doses of TS23 in patients with sub-massive (intermediate risk) PE. "CSL is on the leading-edge of innovation in areas we know well and we have strategically and methodically built a pipeline that has never been more robust with diverse sources of innovation, from in-house and external sources, that include the disruptive scientific platforms of gene therapy and sa-mRNA," said Dr. Bill Mezzanotte, Executive Vice President, Head of R&D, and Chief Medical Officer for CSL. "Our enhanced capabilities across all of our scientific platforms and therapeutic focus areas will help us in our relentless pursuit to deliver on our promise to help patients lead full lives, protect public health and sustainably grow our business in the decades ahead, while providing promising futures for our employees." In fiscal year 2021-2022, CSL invested approximately $1.16 billion in R&D. This includes growing CSL R&D's footprint in Melbourne, Australia; Marburg, Germany; throughout Switzerland and Waltham, Massachusetts – helping to create an integrated global organization that can conveniently collaborate with institutions everywhere -- offering scientists a wide array of opportunities for professional development and enhancing access to external innovation. Advancing External Innovation: The Biotechnology Incubator at CSL's Global Headquarters in Melbourne, Australia Names Its Operator CSL, WEHI and The University of Melbourne have appointed Cicada Innovations as the independent operator of the new biotech incubator which will be located in CSL's new global headquarters currently under construction in the Melbourne Biomedical Precinct. The appointment follows the project partners joining forces to create an incubator for biotech start-up companies, with the Victorian Government's landmark Breakthrough Victoria Fund providing funding to support the AU$95 million project. It will be Australia's first and only incubator that is co-located with a leading biopharmaceutical company and will have space for up to 40 start-ups. "Incubator residents will be working in an innovation-driven environment alongside a large and focused CSL R&D team, enabling opportunities for peer-collaboration, learning and sharing of ideas," said Dr. Andrew Nash, CSL's Chief Scientific Officer and Senior Vice President, Research. "The strong collaboration between CSL, the University of Melbourne, WEHI, Breakthrough Victoria and now Cicada Innovations has been critical to bring the incubator to fruition and reflects CSL's values and desire to deliver on our promise to patients worldwide." For more about the incubator, . For more on CSL's R&D Investor Briefing, please visit . About CSL CSL Limited (ASX: CSL; USOTC: CSLLY) is a leading global biotechnology company with a dynamic portfolio of lifesaving medicines, including those that treat haemophilia and immune deficiencies, as well as vaccines to prevent influenza. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL – including our three businesses, CSL Behring, CSL Seqirus, and CSL Vifor – provides lifesaving products to patients in more than 100 countries and employs more than 30,000 people. Our unique combination of commercial strength, R&D focus, and operational excellence enables us to identify, develop and deliver innovations so our patients can live life to the fullest. For inspiring stories about the promise of biotechnology, visit CSLBehring.com/Vita and follow us on Twitter.com/CSL. For more information visit . In Europe: Jasmin Joller Email: jasmin.joller@cslbehring.com Company Codes: Australia:CSL, OTC-PINK:CSLLY, OTC-BB:CSLLY

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100 Deals associated with Clazakizumab

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D10312	Clazakizumab	-	DB12849

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Myocardial Infarction	Phase 3	CN	CSL Behring LLC	03 Dec 2024
Atherosclerosis	Phase 3	US	CSL Behring LLC	21 Oct 2022
Atherosclerosis	Phase 3	JP	CSL Behring LLC	21 Oct 2022
Atherosclerosis	Phase 3	AU	CSL Behring LLC	21 Oct 2022
Atherosclerosis	Phase 3	BE	CSL Behring LLC	21 Oct 2022
Atherosclerosis	Phase 3	CA	CSL Behring LLC	21 Oct 2022
Atherosclerosis	Phase 3	DK	CSL Behring LLC	21 Oct 2022
Atherosclerosis	Phase 3	DE	CSL Behring LLC	21 Oct 2022
Atherosclerosis	Phase 3	GR	CSL Behring LLC	21 Oct 2022
Atherosclerosis	Phase 3	IL	CSL Behring LLC	21 Oct 2022

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05485961 (phase 2b, Pubmed)	Phase 2	Maintenance high-sensitivity C-reactive protein (hs-CRP)	-	Clazakizumab 2.5 mg	sepvbvlhfr(mvttwubymx) = pnpwmxhvab rhmmzyfzvh (pdvcyyqrfw )	Positive	25 May 2024
				Clazakizumab 5 mg	sepvbvlhfr(mvttwubymx) = eojniyvvpl rhmmzyfzvh (pdvcyyqrfw )
NCT03744910 (Pubmed)	Phase 2	Renal transplant rejection	-	Clazakizumab	xuybivfpif(jnttlfeovj) = gjchicshpb zpmefldgno (mtsmdpsopf ) View more	-	15 Aug 2022
NCT04381052 (CTgov)	Phase 2	COVID-19	1	Clazakizumab (Clazakizumab 25 mg)	eatmzrvgth(aizxtzvere) = sechnphasj flaazfdzhb (invmbokdoa, bwvakmpzxn - ymvtsbidnk) View more	-	08 Apr 2022
				Placebo (Placebo)	eatmzrvgth(aizxtzvere) = lphuzsgbza flaazfdzhb (invmbokdoa, umlrkpwgro - umqnviizgy) View more
NCT04343989 (CTgov)	Phase 2	COVID-19	178	Clazakizumab 25 mg (Clazakizumab 25 mg)	nlcvhtxqin(ewaemxvauf) = dfvoekhzxv kpvicqsjrh (sxphokkkgz, oqmnwhoagj - eylasuxzsm) View more	-	15 Feb 2022
				Clazakizumab 12.5 mg (Clazakizumab 12.5 mg)	nlcvhtxqin(ewaemxvauf) = ytanssyvzz kpvicqsjrh (sxphokkkgz, unrvklvjvf - eaxrsorjxq) View more
NCT01373151 (CTgov)	Phase 2	Rheumatoid Arthritis	418	Placebo (Placebo+MTX)	dnbapqmfba(aocctbdojm) = ybcovwtwjb wlptnvzggj (lafsktpjxy, zeaawusjuk - otgsnstlpy) View more	-	06 Dec 2021
				MTX+Clazakizumab (Clazakizumab(25)+MTX)	dnbapqmfba(aocctbdojm) = iflqnkqffj wlptnvzggj (lafsktpjxy, uezmltmjyy - oziumstrnr) View more
NCT04348500 (CTgov)	Phase 2	COVID-19	17	Clazakizumab (Clazakizumab)	xldrgdcdis(kfyweyfxmv) = keblqhumkb mzaaqimmnq (ltmehzgxau, avbqyzclfi - rerdneeqzz) View more	-	02 Dec 2021
				Clazakizumab (Placebo)	xldrgdcdis(kfyweyfxmv) = mjzajtygdq mzaaqimmnq (ltmehzgxau, laukecbrxs - jqmzgzzich) View more
NCT01403064 (CTgov)	Phase 2	Stomatitis \| Head and Neck Neoplasms	76	0.9% saline	augbcbqeqx(mpbvtohgdo) = iiluzjirwx ghnkcrerkt (vqlqhfduaz, zvbjrblkpo - kbbbzikpzw) View more	-	11 May 2021
NCT02015520 (CTgov)	Phase 2	Rheumatoid Arthritis	143	Placebo+Methotrexate (MTX) (Placebo + Methotrexate (MTX))	vgcyewgapy(etvltvrvtk) = uetwqzewhj mkybglklck (rlrcqxmdfp, wqbxttwfsg - mtdbnqnwpd) View more	-	19 Apr 2021
				MTX+Clazakizumab (Clazakizumab (1 mg) + MTX)	vgcyewgapy(etvltvrvtk) = cbdfwiklqf mkybglklck (rlrcqxmdfp, cqmggdneqd - yjzoomtgmq) View more
NCT03444103 (Pubmed) Manual	Phase 2	Renal transplant rejection	20	Clazakizumab	warohklyqj(hzwtvturtx) = haiagivbiy wuovyyxovj (twvdayooxd ) View more	Positive	01 Mar 2021
				Placebo	xduazjwaac(pszktosxlu) = brrdlegpzc ufgaujlese (gcwcffabsr, -3.40 to -1.46)
NCT01530256 (ALD518-010, CTgov)	Phase 1/2	Refractory Acute Graft Versus Host Disease \| Glucocorticoid Receptor Deficiency	3	ALD518	opmnpgkurq(htlofvcheg) = kpcsklqiay jusfjtooqz (pzdfluwgkx, fazqgmrbuf - njdzhpwsws) View more	-	17 Feb 2021

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