Aeterna Zentaris Achieves Proof-of-Concept for the Treatment of NMOSD with AIM Biologicals Program

– Company advancing AIM Biologicals development program as a potential therapeutic treatment option for neuromyelitis optica spectrum disorder (“NMOSD”)

Positive results presented at the 13thInternational Congress on Autoimmunity being held in Athens, Greece

Preliminary data with mouse 2D2 models of spontaneous autoimmune encephalomyelitis (EAE) indicate that mouse-adapted AIM Biologicals may reduce optic neuritis, loss of inner nuclear layer neurons and EAE symptoms

TORONTO, ONTARIO, June 13, 2022 (GLOBE NEWSWIRE) — Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZS) (“Aeterna” or the “Company”), a specialty biopharmaceutical company developing and commercializing a diversified portfolio of pharmaceutical and diagnostic products, today announced its Autoimmunity Modifying (“AIM”) Biologicals program has achieved pre-clinical proof-of-concept for the potential treatment of neuromyelitis optica spectrum disorder (“NMOSD”) (also known as “Devic disease”), a chronic autoimmune disorder of the brain and spinal cord dominated by inflammation of the optic nerve and spinal cord and which can be fatal in approximately 30% of patients within five years of diagnosis. These findings were presented at the 13th International Congress on Autoimmunity being held June 10-13, 2022 in Athens, Greece.

The abstract presented at the Congress, titled “Antigen presentation on MHC class Ibrelated molecules induces Aquaporin-4-specific regulatory T cells in PBMC and prevents experimental autoimmune encephalomyelitis in mice, was presented in a poster format and as an oral presentation by Aeterna’s research collaborator, Valentin Bruttel, PhD, Senior Researcher, Department of Obstetrics and Gynecology, School of Medicine, University of Wuerzburg (“the University”).

“There remains strong unmet medical need to provide treatment options for patients diagnosed with NMOSD, a rare but potentially devastating autoimmune condition. Given the severe impact NMOSD can have on people, we are very encouraged by the proof-of concept our AIM Biologicals program has demonstrated in both in vitro and mouse models,” said Dr. Klaus Paulini, Chief Executive Officer of Aeterna. “We are grateful for the collaborative work being done with Dr. Bruttel, Prof. Wischhusen and their team, and we look forward to continue further developing Aeterna’s AIM Biologicals for the potential treatment of NMOSD.”

Aquaporin-4 (AQP-4) is the autoimmune antigen implicated in neuromyelitis optica (NMO), a demyelinating and inflammatory autoimmune disorder of the central nervous system (CNS). AIM Biologicals are based on a mechanism that is physiologically important for feto-maternal immune tolerance during pregnancy. These new biomolecules utilize the α3 domain of the human MHC class Ib molecule HLA-G to inhibit antigen-specific T cells via the human ILT-2 or the murine PIRB receptor. As part of Aeterna’s ongoing pre-clinical studies in collaboration with the University, researchers at the University generated fusion proteins comprising an AQP-4-derived antigenic peptide, MHC class I α1-α2 antigen presenting domains, the HLA-G α3 domain and b2-microglobulin to investigate whether these novel single-chain biomolecules can induce antigen-specific tolerance towards presented AQP-4 and other neuroinflammatory peptide antigens. Various AIM Biologicals were then tested and shown to induce antigen-specific regulatory T cells (Treg) in vitro and to inhibit CD8+ driven experimental autoimmune encephalomyelitis (EAE) models and optic neuritis in 2D2 mice in vivo.

“We are very pleased with these pre-clinical proof-of-concept results which help to inform our research moving forward to define a development candidate. As demonstrated in these pre-clinical studies, we believe that Aquaporin-4-specific AIM Biologicals have the potential to provide targeted immunosuppression in NMOSD. We look forward to advancing this important program with our exclusive licensee, Aeterna, to potentially meet an indication where there remains unmet medical need,” added Dr. Bruttel, who has just received the audience prize and the German innovation award at the recent German Biotechnology Days 2022.

Summary of Key Highlights

  • HLA-G elicits specific tolerance towards presented peptides. AIM Biologicals use this mechanism to induce tolerance to autoimmune antigens.
  • Mouse-adapted AIM Biologicals molecules selectively induce IL-10, inhibit IFN-γ secretion in cognate T cells, inhibit EAE symptoms and spinal cord inflammation.
  • Mouse-adapted AIM Biologicals constructs presenting MOG44 peptide elicit a strong bystander immunosuppression in OT-I ODC-Ova mice models and prevent EAE and MOG-specific autoantibodies in CD4+ T cell driven MOG EAE models.
  • AQP4_HLAG AIM Biologicals induce IL10-secreting CD8+CD28CD127 Treg in hPBMC.
  • Preliminary data with mouse 2D2 models of spontaneous EAE indicate that mouse-adapted AIM Biologicals may reduce optic neuritis, loss of inner nuclear layer neurons and EAE symptoms.

The poster can be accessed on the Publications page of the Company’s website.

About Neuromyelitis Optica Spectrum Disorder (NMOSD)

NMOSD is an antibody mediated inflammatory central nervous system (“CNS”) disorder that affects about one per 100,000 population per year. NMOSD, also known as Devic’s disease, is a chronic disorder of the brain and spinal cord dominated by inflammation of the optic nerve (optic neuritis) and of the spinal cord (myelitis). Typical symptoms include vision loss, muscle spasms, paraparesis, and incontinence. If left untreated, 50% of individuals with NMOSD may become wheelchair bound and blind, and 30% may have died within five years after the first attack. The water channel protein AQP4 is widely expressed in the brain, spinal cord, and optic nerves. Auto-antibodies directed against AQP4 play an important role in the pathogenesis of NMOSD.

Currently there are only three approved medications available for the treatment of NMOSD, all with very high annual treatment costs and the risk of the patient contracting serious infections. Therefore, the Company believes there remains a strong medical need to offer new therapeutic options to the patients.

In the U.S. and Europe there are currently approximately 10,000 to 15,000 patients living with NMOSD. Of these the AQP4 antibody seropositive patients who represent about 80% of the NMOSD population are the targeted patients for a potential therapy based on the AIM Biologicals technology.

About AIM Biologicals

AIM Biologicals are targeted, highly specific autoimmunity modifying therapeutics. This platform technology utilizes a mechanism that is physiologically required for “feto-maternal immune tolerance” during pregnancy. Despite 50% paternal antigens, the maternal immune system tolerates a fetus, while protection against pathogens is retained. This requires selective tolerance induction against fetal antigens. During pregnancy, this goes along with an amelioration of autoimmune diseases.

AIM Biologicals utilize a novel technique which is based on the presentation of antigens on immunosuppressive MHC class I molecules to selectively and efficiently induce antigen-specific tolerance. Based on this mechanism, targeted immunomodulatory therapeutics are designed as optimized soluble molecules and adapted to selectively induce tolerance to various autoantigens. Pre-clinical studies conducted thus far indicate that tolerance induction may be achieved via selective elimination of antigen-specific immune effector cells and via induction of antigen-specific regulatory T cells from naïve T cells.

For the potential treatment of NMOSD, AIM Biologicals presenting a specific antigen derived from the water channel protein aquaporin-4 (AQP4) loaded onto a soluble immunoregulatory HLA-G protein has the potential to selectively induce immunological tolerance in the central nervous system. AIM Biologicals thus have the potential to become highly specific and effective yet not personalized treatment options for NMOSD.

About Aeterna Zentaris Inc.

Aeterna Zentaris is a specialty biopharmaceutical company developing and commercializing a diversified portfolio of pharmaceutical and diagnostic products focused on areas of significant unmet medical need. The Company’s lead product, macimorelin (Macrilen™; Ghryvelin®), is the first and only U.S. FDA and European Commission approved oral test indicated for the diagnosis of adult growth hormone deficiency (AGHD). The Company is leveraging the clinical success and compelling safety profile of macimorelin to develop it for the diagnosis of childhood-onset growth hormone deficiency (CGHD), an area of significant unmet need, in collaboration with Novo Nordisk.

Aeterna Zentaris is dedicated to the development of therapeutic assets and has recently taken steps to establish a growing pre-clinical pipeline to potentially address unmet medical needs across a number of indications, including neuromyelitis optica spectrum disorder (NMOSD), Parkinson’s disease (PD), hypoparathyroidism and amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease). Additionally, the Company is developing an oral prophylactic bacterial vaccine against SARS-CoV-2 (COVID-19) and Chlamydia trachomatis.

For more information, please visit www.zentaris.com and connect with the Company on Twitter, LinkedIn and Facebook.

Forward-Looking Statements

This press release contains statements that may constitute forward-looking statements within the meaning of U.S. and Canadian securities legislation and regulations and such statements are made pursuant to the safe-harbor provision of the U.S. Securities Litigation Reform Act of 1995. Forward-looking statements are frequently, but not always, identified by words such as “expects,” “anticipates,” “believes,” “intends,” “potential,” “possible,” and similar expressions. Such statements, based as they are on current expectations of management, inherently involve numerous risks, uncertainties and assumptions, known and unknown, many of which are beyond our control. Forward-looking statements in this press release include, but are not limited to, those relating to: expectations regarding the potential of AIM Biologicals, to the potential to provide targeted immunosuppression, to be a highly specific and effective treatment for NMOSD and the Company’s ability to conduct pre-clinical research to identify and characterize an AIM Biologicals-based development candidate for the treatment of NMOSD.

Forward-looking statements involve known and unknown risks and uncertainties, and other factors which may cause the actual results, performance or achievements stated herein to be materially different from any future results, performance or achievements expressed or implied by the forward-looking information. Such risks and uncertainties include, among others, results from ongoing or planned pre-clinical studies of our products under development may not be successful or may not support advancing the product to human clinical trials; our ability to raise capital and obtain financing to continue our currently planned operations; our now heavy dependence on the success of Macrilen™ (macimorelin) and related out-licensing arrangements and the continued availability of funds and resources to successfully commercialize the product, including our heavy reliance on the success of the license agreement and the amended license agreement (collectively the Novo Amended License Agreement); the global instability due to the global pandemic of COVID-19 and the war in the Ukraine and the resulting geopolitical instability, and its unknown potential effect on our planned operations; our ability to enter into out-licensing, development, manufacturing, marketing and distribution agreements with other pharmaceutical companies and keep such agreements in effect; and our ability to continue to list our common shares on the NASDAQ. Investors should consult our quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties, including those risks discussed in our Annual Report on Form 20-F and annual information form, under the caption “Risk Factors”. Given the uncertainties and risk factors, readers are cautioned not to place undue reliance on these forward-looking statements. We disclaim any obligation to update any such factors or to publicly announce any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, unless required to do so by a governmental authority or applicable law.

No securities regulatory authority has either approved or disapproved of the contents of this news release. The Toronto Stock Exchange accepts no responsibility for the adequacy or accuracy of this release.

Investor Contact:

Jenene Thomas
JTC Team
T (US): +1 (833) 475-8247
E: [email protected]


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