Antiferon (interferon alpha kinoid) / Chong Kun Dang, Neostell, 3PBIOVIAN, Neovacs, Centurion Pharma, BioSense Global, Edesa Biotech - LARVOL DELTA

IMMUNE AND TRANSCRIPTOMIC DYNAMICS IN LUPUS NEPHRITIS ASSOCIATED WITH INTERFERON α KINOID TREATMENT (EULAR 2025) - "Specifically, it focuses on patients treated with interferon α kinoid (IFN-K), a therapeutic vaccine designed to neutralize interferon α subtypes, which has shown potential to reduce disease manifestations in SLE [4]... The present study highlights the effects of interferon α kinoid treatment on lupus nephritis by demonstrating significant reductions in plasma cell proportions and disease activity over time, as reflected by decreased SLEDAI scores. While only ISG15 showed a significant decrease in gene expression at 6 months, changes in immune cell populations further support the immunomodulatory effects of the treatment. However, limitations such as the small sample size, lack of clinical data, and the secondary nature of the analysis warrant further research to validate these findings and explore their implications in different disease states and treatment contexts."

Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Rheumatology • Systemic Lupus Erythematosus • IFI27 • IFNA1 • MX1 • RSAD2

The Cellular and Spatial Type I Interferon Response Following Skin Exposure to Ultraviolet Light (ACR Convergence 2023) - "And 3) What are the different Type I IFNs (IFN-a, IFN-b, IFN-k) being made after UV exposure?... We have identified the spatial locations of different IFN-I species in the skin following UV light injury. Copy number was highest in the epidermis for IFN-ac. Spatial transcriptomics also illuminates differences in inflammatory versus metabolic programs that are activated in immune (CD45) versus epidermal (cytokeratin positive) and dermal locations."

Graft versus Host Disease • Immunology • Inflammation • Inflammatory Arthritis • Lupus • IFIT1 • IFNA1 • ISG15 • PTPRC

Keratinocyte VISTA Suppresses Skin IFN-I Production by Regulating DNA Damage Repair and Cytosolic DNA Sensing (ACR Convergence 2023) - "Vsir-/- skin had increased IFN-k mRNA, IFN-b protein, as well as total STING protein levels (Fig... These studies identify VISTA as a suppressor of IFN-I production in keratinocytes and demonstrate STING-dependent IFN-I production in the absence of VISTA. As oxidized DNA is resistant to degradation in the cytosol where it can serve as a potent trigger of cGAS-STING, VISTA promotion of DNA repair may indirectly suppress STING signals. Antibody-mediated activation of VISTA in keratinocytes demonstrates its potential as a target to suppress IFN-I production in the context of photosensitivity and lupus."

Dermatology • Immunology • Inflammatory Arthritis • Lupus • KRT14 • OGG1 • VSIR

Immune checkpoint VISTA regulates DNA sensing and repair pathways that contribute to type I interferon (IFN-I) production in the skin (P828) (IMMUNOLOGY 2023) - "Together, this study identifies VISTA as a novel regulator of IFN-I production, by modulating DNA damage repair and sensing. The keratinocyte-intrinsic role of VISTA is therapeutically relevant as lupus keratinocytes express high IFN-k and are direct targets of UV-induced DNA damage."

Immune Modulation • Immunology • Inflammatory Arthritis • Lupus • IGF2BP1 • VSIR

Human papilloma virus infection as an antigenic stimulus in psoriasis (PsoriasisG2C 2021) - "IFN-k, a type III IFN, is important in the innate antiviral response and was also increased in psori-asis skin. Our findings support the hypothesis that HPV may act as an antigenic stimulus in psoriasis."

Dermatology • Epstein-Barr Virus Infections • Immunology • Infectious Disease • Inflammation • Oncology • Psoriasis • IL17A • PCR

Therapeutic Potential of Anti-Interferon α Vaccination on SjS-Related Features in the MRL/lpr Autoimmune Mouse Model. (PubMed, Front Immunol) - "Hence, we assessed the immunogenicity, efficacy, and tolerance of IFN-Kinoid (IFN-K), an anti-IFNα vaccination strategy, in a well-known mouse model of systemic autoimmunity with SjS-like features: MRL/MpJ-Faslpr/lpr (MRL/lpr) mice...No adverse effects were observed. We herein report on the strong efficacy of an innovative anti-IFNα vaccination strategy in a mouse model of SjS, paving the way for further clinical development (a phase IIb trial has just been completed in systemic lupus erythematosus with promising results)."

Journal • Preclinical • Immunology • Inflammatory Arthritis • Lupus • Pain • Sjogren's Syndrome • Systemic Lupus Erythematosus • IFNA1

Blood Genomics Identifies Three Subtypes of Systemic Lupus Erythematosus: "IFN-High," "NE-High," and "Mixed". (PubMed, Mediators Inflamm) - "Our research results indicated that identifying the molecular mechanism associated with different SLE subtypes would benefit the molecular diagnosis and stratified therapy. Moreover, repositioning of IFN-K based on subtypes also revealed an improved therapeutic effect, providing a new direction for disease treatment and drug development."

Journal • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Pediatrics • Systemic Lupus Erythematosus • IFNA1

Safety of IFNa kinoid in systemic lupus erythematosus -

P1/2, N=28

NEOVACs' IPO on the alternate exchange of NYSE euronext (Neovacs) -

Target amount to be raised in the IPO is reduced to ?11M, vs. ? 20M initially planned; Funds will be used for conducting P2 trial of IFN-kinoid for lupus

IPO funds

Neovacs announces closing of 7.5 M Euro capital increase with U.S. investors (Neovacs Press Release) - "The proceeds of the capital increase will provide additional funding to the Company to finance the development plan of IFNα-Kinoid, including: A phase IIb clinical trial of IFNα-Kinoid in lupus conducted in Europe, Latin America and Asia, to begin in the second half of 2015; and A phase IIa clinical trial of IFNα-Kinoid in lupus conducted in the United States."

Financing • Immunology • Lupus

Safety of IFNa kinoid in systemic lupus erythematosus (clinicaltrials.gov) - P1/2, N=28; Active, not recruiting; Completion date: Dec 2011 -> Aug 2013

Trial completion date • Immunology • Lupus

IFN-K-001 phase I/II study in lupus: final results presented today at the American College of Rheumatology (ACR) Annual Scientific Meeting in Chicago in both an ACR press conference and oral session (Neovacs) - P1/2, N=28; IFN-K-001; Neovacs announced results of its IFN-K-001 clinical study in lupus, presented at ACR Annual Scientific Meeting; Detailed analysis of study shows that 100% of pts who received IFNα-Kinoid produced antibodies to IFNα; It also shows that administration of IFNα-Kinoid, especially at higher doses, 120mcg & 240mcg, has statistically significant (p=0.0001) impact on dysregulation of genes related to interferon α (interferon signature) as well as those associated with lupus disease (lupus signature); Antibodies to IFNα raised by IFNα-Kinoid have significant impact on multiple disease markers; Activity of antibodies to IFNα induced by Kinoid administration is confirmed by fact that reduction in dysregulation of lupus-associated genes is clearly observable

P1/2 data • Immunology

Neovacs obtains South Korea health authority approval for IND application with IFNα kinoid in lupus (Neovacs Press Release) - P2b, N=166; NCT02665364; Sponsor- Neovacs; “NEOVACS…today announced that South Korea health authority approved Neovacs’s Investigational New Drug application for IFNα Kinoid in phase IIb development in Lupus…The results of this trial are expected for summer 2017.”

Anticipated P2b data • IND • Immunology • Lupus

Neovacs initiates clinical program in dermatomyositis (GlobeNewswire) - "NEOVACS...today announced the launch of its clinical development program in Dermatomyositis (DM), an orphan skin and muscular condition with significant unmet medical need....The decision follows a recommendation earlier this year by the Company's Scientific Advisory Board to pursue IFNα-Kinoid as a potential treatment for DM...Neovacs plans to conduct a multicentric phase I/IIa trial of IFNα-Kinoid in adult DM in 15 patients which is anticipated to launch in early 2016 in France and other European countries."

Anticipated new P1/2 trial • Immunology

Neovacs issued new broad patent in China for IFNα Kinoid (GlobeNewswire) - "Neovacs...today announces that it has been granted a new patent from the Chinese Patent Office (SIPO), titled: 'Method of treatment of a disease related to the overexpression of IFNα...This new patent has been also filed in all major markets in the world, to cover the use of Neovacs’ IFNα Kinoid vaccine for all diseases characterized by an overexpression of the cytokine, Interferon alpha (IFNα), including Lupus, Dermatomyositis and Type 1 diabetes. This patent provides a strong protection until at least 2032."

Anticipated patent expiry • Patent • Immunology • Lupus

IFNα kinoid: Anticipated launch and approval in US, Europe and China for SLE in 2020 (Neovacs) - Analyst Report

Anticipated BLA • Anticipated EU regulatory • Anticipated launch Europe • Anticipated launch non-US • Anticipated launch US • Anticipated non-US regulatory • Lupus

Active immunization against IFNα with IFN-kinoid in SLE patients is safe, immunogenic and induces down-regulation of IFN- mediated genes (ACR/ARHP 2011) - P1/2, N=28; Patients with a positive signature have significantly higher dsDNA Ab titers and significantly lower C3 and C4 levels ; Study showed positive immune and pharmacodynamic results with active immunotherapy against Interferon-α in the treatment of SLE

P1/2 data • Immunology

Neovacs aims to complete recruitment for research (Investing.com) - P2, N=178; NCT02665364; Sponsor: Neovacs; "Neovacs plans to partner IFN-K, implying possible launches in 2021...Neovacs is aiming to complete recruitment into the 178-patient Phase IIb by late summer 2016, with an expected June 2017 release of preliminary data...Neovacs intends to find a partner to run and fund Phase III studies from 2018. This could enable a US and EU regulatory filing by 2020 and possible marketing from 2021.

Anticipated enrollment status • Anticipated EU regulatory • Anticipated launch Europe • Anticipated launch US • Anticipated licensing / partnership • Anticipated new P3 trial • Anticipated P2b data • Anticipated regulatory • Lupus

Neovacs provides corporate update and reports full-year 2017 financial results (GlobeNewswire) - P2b, N=185; NCT02665364; Sponsor: Neovacs; "Completed patient enrollment in phase the IIb clinical study of IFNalpha Kinoid in lupus...top-line results are currently expected end of June 2018...Neovacs intends to begin executing on its action plan for 2018...Validated with healthcare authorities  globally the registration strategy  to conduct the lupus Phase III clinical program."

New P3 trial • P2b data • Immunology • Lupus

Neovacs: Investor Presentation (Neovacs) - “Good safety profile of IFNα-Kinoid at each dose level (few local or systemic reactions, only one flare reported as SAE)”; “All patients developed binding anti-IFNα antibodies. Higher production of binding and neutralizing antibodies in patients with more severe lupus”; “Those antibodies neutralize all 13 subtypes of IFNα, in contrast with monoclonal anti-IFNα antibodies (2 subtypes only are completely neutralized)”; “Improvement of disease biomarkers (IFN signature & C3) is correlated with the intensity and duration of the neutralizing response”; “Follow up until decline of anti-IFNα antibodies of 5 patients with a tapering in CS and no flare 3 years after dosing”

P1/2 data • Immunology • Lupus

Serum IFN alpha, but not IFN beta or IFN omega, correlates with IFN signature in SLE patients (EULAR 2014) - Presentation time: 12.06.2014, 12:00; Abstract #THU0040; P1/2, N=28; NCT01058343; Sponsor:Neovacs; "IFNα, IFNβ and IFNω are detected in the sera of patients with SLE. IFNα and IFNβ/ω are not regulated similarly. Serum IFNβ is significantly associated with mucocutaneous involvement, while serum IFNα is higher in more active disease. The IFN signature score observed in SLE whole blood cells is driven by IFNα."

Biomarker • Immunology • Lupus

Neovacs provides corporate update and reports full year 2016 financial results (GlobeNewswire) - P2b, N=178; NCT02665364; Sponsor: NEOVACS; "NEOVACS...today provided a corporate update and announced its full-year 2016 financial results, as approved by its Board of Directors on March 29, 2017...The Phase IIb clinical study already has enrolled more than 80% of its target number of 178 patients. The Independent Data Safety Monitoring Board (iDSMB) issued a favorable opinion for the continuation of the Phase IIb clinical study in January 2017."

DSMB • Enrollment status • Immunology • Lupus

Neovacs: HY 2015 Results (Neovacs) - Anticipated filing of IND for P2a trial in SLE in US in early 2016; Anticipated initiation of P1/2a trial (N=30) in adult dermatomyositis in 2016; Anticipated data from P2b IFN-K-002 trial in SLE in Q1 2017

Anticipated IND • Anticipated new P1/2 trial • Anticipated P2b data • Immunology • Lupus

Antiferon: Protection of use/method patents in China, US, Russia, EP, Australia, Mexico, Hong Kong, Canada, Japan, Brazil, Israel, India, South Korea until 2032 (Neovacs) - Corporate Presentation

Patent • Immunology • Lupus

Antiferon: Protection of composition-of-matter patents in EP, US until 2020 (Neovacs) - Corporate Presentation: Protection of composition-of-matter patents in EP, US, China, Canada, South Africa, Australia, Japan, Brazil, India, New Zealand until 2023; Protection of composition-of-matter patents in EP, US, Canada, Japan until 2024

Patent • Immunology • Lupus