Dr. Klaus Paulini reports

AETERNA ZENTARIS OUTLINES PROGRESS ON DEVELOPMENT PIPELINE PROGRAMS AND PROVIDES CORPORATE UPDATE

Aeterna Zentaris Inc. has provided an update on its therapeutic and diagnostic development pipeline programs, and outlined upcoming key milestones.

"We are encouraged by our significant progress across all of our active development programs and, based on the prioritization of our pipeline, have strengthened our focus on our diagnostic and therapeutic programs as we execute on key decision points," commented Dr. Klaus Paulini, chief executive officer of Aeterna. "Additionally, in our ongoing Detect clinical trial, we are making significant progress regarding patient recruitment and believe we are well positioned to continue building momentum towards completion of the study by year's end. Further, based upon our active outreach and discussions, we expect to secure an alternate development and commercialization partner for Macrilen for the U.S. and Canada."

Therapeutics development pipeline update

Autoimmunity modifying (AIM) biologicals: Targeted, highly specific autoimmunity modifying fusion proteins for the potential treatment of neuromyelitis optica spectrum disorder (NMOSD) and Parkinson's disease (PD)

AIM biologicals represent a unique platform technology with the potential to address the cause, and not only the symptoms, of autoimmune and inflammatory, neurodegenerative disorders at early stages. This approach is based on induction of selective and highly target-specific immune desensibilization based on the natural concept of feto-maternal tolerance.

Dr. Paulini added: "We have received encouraging feedback from our collaborator and scientific adviser on the NMOSD indication, Dr. Michael Levy, research director of the division of neuroimmunology and neuroinfectious disease at Massachusetts General Hospital. Dr. Levy shares our vision that presenting antigens on soluble HLA-G fusion proteins is a promising, novel approach to induce antigen-specific immune tolerance among NMOSD and PD patients. Together, we look forward to furthering the development of this program."

Recent highlights:

• Demonstrated positive preclinical proof-of-concept in various in vitro and in vivo models.
• In-depth profiling of a limited set of candidates for potential use in clinical development.
• Confirmed AIM biologicals' mechanism of action and efficacy in ex vivo studies in human blood samples from both NMOSD and PD patients.

Next steps:

• Evaluation of manufacturing strategy and initiation of production of selected development candidates.
• Continuing compilation of a comprehensive preclinical data package for scientific advice meetings with regulatory authorities, expected to take place in the near future.

Delayed-clearance parathyroid hormone (DC-PTH, AEZS-150) fusion proteins: Potential treatment for chronic hypoparathyroidism

AEZS-150 is a fusion protein of PTH [1-34] coupled to a modified human growth-hormone binding protein (GHBP). Preclinical results so far indicate the potential for maintaining regular calcium and phosphate levels in blood longer and more consistently than with current treatments. This project aims to address this debilitating orphan disease, which is currently without satisfactory treatment options, with weekly instead of daily injections.

"There is a major unmet need for physiological parathyroid hormone replacement in patients with hypoparathyroidism, either congenital or acquired from neck surgery, who have an impaired quality of life, and increased morbidity and mortality on current therapy. DC-PTH will address this unmet need," commented Professor Richard Ross, MD, FRCP, department of oncology and metabolism at Sheffield University (United Kingdom). "Aeterna has made great progress in the manufacturing process development of AEZS-150 and repeating validation studies in models of hypoparathyroidism required before undertaking trials in patients."

Recent highlights:

• Detailed profiling of AEZS-150 through in vitro studies and in vivo models of hypoparathyroidism.
• Established a master cell bank for a cell line expressing AEZS-150 in good yield.
• Continued progress in the development of a production process suitable for larger scale GMP (good manufacturing practice) manufacturing.

Next steps:

• Meet with regulatory authorities to determine the development path forward. The company expects such a meeting in Q4 2023 and, as outcome, an abbreviated safety and toxicology program as the active principle ([1-34]-PTH fragment) is already approved and in use.
• Initiate IND (investigational new drug)-enabling preclinical studies in 2024.

Macimorelin therapeutic (AEZS-130): Ghrelin agonist in development for the treatment of ALS (Lou Gehrig's disease)

Amyotrophic lateral sclerosis (ALS) is a debilitating and deadly orphan disease, and those who suffer from this terminal condition have few treatment options. Macimorelin's (AEZS-130) multiple modes of action should have the potential to improve the quality of life for these patients.

Recent highlights:

• Successful development of an alternative formulation suitable for use in ALS.
• Accumulating data for positive effects of AEZS-130 treatment on survival of motor neurons.
• Continued assessment of AEZS-130 in transgenic mouse ALS models and in human patient-derived neuron cultures.
• Completion of initial toxicology and safety studies to support clinical development as a therapeutic, in addition to the already existing body of safety and toxicology data from the company's macimorelin diagnostic development.

Next steps:

• Following achievement of proof-of-concept, the company will seek to have a scientific advice meeting with regulatory authorities to discuss program development next steps.
• Completion of toxicology and safety studies to support treatment over prolonged periods.

Diagnostics development and commercialization update

Macimorelin diagnostic: Approved and commercialized as test for adult growth hormone deficiency and in clinical phase 3 development for childhood-onset growth hormone deficiency (CGHD) testing.

Aeterna is currently conducting its pivotal phase 3 safety and efficacy study AEZS-130-P02 (the Detect trial) evaluating macimorelin for the diagnosis of childhood onset growth hormone deficiency. Most clinical sites in the United States, as well as European countries, are open for patient recruitment.

Recent highlights:

• Phase 3 study: Significant progress made with Detect patient recruitment, also by engagement of an additional clinical research organization (CRO). Currently three new countries (Armenia, Slovakia and Turkey), have continuing Detect clinical trial application activities and almost half the foreseen subjects have meanwhile concluded the trial.
• Macimorelin commercialization: Having regained full rights to Macrilen for the U.S. and Canada from Novo Nordisk in May, 2023, the company is actively focused on identifying an alternate development and commercialization partner for Macrilen for U.S. and Canada.

"We continue to manage our cash responsibly with a balanced derisked development approach, which we believe enables us to optimize the company's capital and human resources," added Giuliano La Fratta, chief financial officer of Aeterna. "We remain focused on advancing our programs to their next phase of development, guided by the data and financial risk/reward as we do so. Based on our current projections, we believe the company has the ability to meet its currently anticipated cash needs into 2025."

About Aeterna Zentaris Inc.

Aeterna 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. Food and Drug Administration- 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.

Aeterna is dedicated to the development of its therapeutic asset and has established a preclinical development pipeline to potentially address unmet medical needs across a number of indications, including neuromyelitis optica spectrum disorder, Parkinson's disease, hypoparathyroidism and amyotrophic lateral sclerosis (Lou Gehrig's disease).

We seek Safe Harbor.