Aviceda Therapeutics Inc.
Glyco-immuno Therapeutics, The Next Bio-pharmaceutical Frontier

All cells and organisms are covered with a dense layer of glycans (sugars) called the glycome used by the immune system to identify healthy, damaged, or foreign cells. In diseases of chronic age-related inflammation like macular degeneration and Alzheimer, the glycome has become unrecognizable, so immune cells do not recognize the “do not” eat me signal and these pacman like immune cells eat both healthy and damaged retinal and brain cells. In disease of acute inflammation like sepsis, cytokine storm (Covid-19) or acute respiratory distress syndrome there are too many activating sugar signals (spike protein) and inadequate deactivating sugar (sialic-acid) signals causing intense inflammation and death. In diseases like cancer, the cancer cell cloaks itself with healthy appearing sugars (sialic-acid) that represent the do not attack me signal to the immune system resulting in unchecked growth of cancer. In diseases of fibrosis, like blood, lung, and liver fibrosis the healing immune cells continuously produce scar tissue and do not have a stop producing scar tissue signal resulting in deadly fibrosis.

The holy grail in immune modulation is to break this glyco-code and develop a therapeutic that can hack into and control the body’s immune system potently and specifically. To hack into and turn off an immune cell, we need to present a specific sialic-acid pattern (self glyco-code) to a check point receptor called a sialic-acid-binding immunoglobulin-type of lectins (Siglecs) when agonized, will resolve all forms of inflammation. Aviceda Therapeutics, a private clinical-stage biotechnology company, has developed the largest library of natural and proprietary synthetic glycans (glyco-codes) that can be rapidly synthesized and conjugated to a nanoparticle producing therapeutics that can modulate the innate, adaptive, and complement immune system (hacker) by presenting a correctly oriented high-affinity sialic acid pattern. This proprietary high-affinity ligands of Siglecs (HALOS™) platform weaponizes sugars in the war against diseases like macular degeneration, diabetic retinopathy, Alzheimer’s, multiple sclerosis, acute respiratory distress syndrome, myelofibrosis, idiopathic pulmonary fibrosis, fatty liver diseases, transplant rejection, allergies, and cCancer. The development of the HALOS therapeutic platform makes Aviceda a pioneer, architect, and leader of the glyco-therapeutic biotechnology revolution.

“The biopharmaceutical industry needs better immune modulating drugs that put the brakes on inflammation. Our technology mimics the physiological immune resolving glyco-code that can directly deactivate the immune system, specifically and profoundly,” Michael Tolentino, MD, Chief Technology Officer and Co-founder, Aviceda Therapeutics Inc. & Aviceda Glycotech Ltd.

Pioneering Glyco-Therapeutic for Age-Related Macular Degeneration.

The complications of age-related macular degeneration (AMD) are the leading cause of blindness in the elderly and the developed world. While intravitreal injections for macular neovascularization, a therapy pioneered by Aviceda’s co- founders, provides hope for those afflicted in their golden years, these injections do not address the underlying cause of the disease and do not provide therapeutic benefit for dry macular degeneration and geographic atrophy (advanced form of AMD).

Geographic atrophy, which is the loss of retinal cells due to destruction and clearance by chronic unchecked activated macrophage (pacman) immune cells, is a blinding complication that can develop in all macular degeneration patients even those treated for macular neovascularization.

“We aim to directly stop the immune destruction and phagocytosis of retinal cells that results in blinding geographic atrophy with AVD-104”

Aviceda Lead Ocular asset, AVD-104, is a sialic-acid mimetic nanoparticle designed to put the brakes on complement inflammation, macrophage phagocytosis, and immune cell VEGF production. It has demonstrated a robust in-vitro/vivo efficacy resolving macrophage activation and inhibiting complement amplification with the potential for every 4- 6-month intraocular dosing. Superior safety was demonstrated in a GLP fashion in multiple animal models including non-human primates. All animal studies demonstrated excellent safety and no sign of intra-ocular inflammation or local and systemic toxicity. In addition, AVD-104 has demonstrated equivalent prevention of neovascularization compared to aflibercept (Eylea^®) in a well-established ocular model of macular neovascularization. IND for AVD-104 has been initiated and the Phase II “Siglec trial” has begun recruiting patients.

“Checkpoint inhibition revolutionized cancer therapy, our platform technology can target the protein and glyco-immune checkpoint pathway with bi-specific functional therapeutics without off-target effect”

“We aim to directly stop the immune destruction and phagocytosis of retinal cells that results in blinding geographic atrophy with AVD-104,” says David Callanan, MD, Chief Medical Officer of Aviceda Therapeutics Inc.

Glyco-immune-checkpoint inhibitors: A Cancer Breakthrough.

The human body is producing cancer cells constantly, but the immune system recognizes, attacks, and clears these cells before they can harm the host. Cancer cells that evade the immune system can lead to unchecked growth and metastases. Cancers evade the immune system by secreting mucous or presenting on the cell surface a sialic acid (self-sugar) pattern that stop immune cells from attacking, akin to a feverless Covid patient allowed to board a plane to the United States.

Immune cells have checkpoint pattern recognition receptors that examine sugar patterns on cells that are encountered during immune surveillance in order to quarantine (inflammation) or let pass (no inflammation) the encountered cell. The most recognized checkpoint receptor that has revolutionized cancer immunotherapy is called programmed cell death-1 receptors (PD-1) which binds a sialylated glycoprotein called programmed cell death ligand -1 (PDL-1). Siglecs are the largest family of PD-1 like powerful checkpoint receptors that cancers use to evade immune attack. But unlike PD-1 they are a family with 17 members, are distributed selectively on all immune cells, and only bind to correctly presented sialic-acid patterns.

The prevention of binding between PD-1 and PDL-1 with antibody called Keytruda initiated the first wave of immunotherapies for Cancer. Aviceda Glycotech a Belfast Ireland subsidiary of Aviceda is developing Siglec/PD-1 checkpoint inhibitors that can block Siglecs selectively or block both PD-1 and Siglecs. The ability to block all the glyco-immune checkpoint pathways should expand the efficacy of checkpoint inhibitor immunotherapy into tumors such as pancreatic and lung cancer that are not responsive to PD-1 blockade alone.

This next generation of pan specific multi checkpoint glycan inhibitors invented and pioneered by Aviceda is being developed by Belfast based subsidiary Aviceda Glycotech. This dual mode therapeutic strategy should revolutionize cancer immunotherapy for those patients partially or nonresponsive to singular checkpoint blockade.

“Checkpoint inhibition revolutionized cancer therapy, our platform technology can target the protein and glyco-immune checkpoint pathway with bi-specific functional therapeutics without off-target effects,” says Christopher Scott, PhD, Chief Scientific Officer and Scientific Co-Founder Aviceda Therapeutics Inc. & Aviceda Glycotech Inc.

Industry Leading Platform and Team.

Aviceda has developed expertise and intellectual property that has exclusive rights to the world’s largest library of relevant glycans, a fully automated glycan synthesizer, methods for high throughput screening of high affinity lectin binding ligands, bio-orthogonal conjugation chemistry and rapid glycomimetic nanoparticle therapeutic development and manufacturing technology. Aviceda’s executives are serial biotech entrepreneurs and experienced bio pharma executives who are experts in drug development and clinical trials. Aviceda’s clinician scientists and scientific advisors are the pioneers in ophthalmology, oncology, glycobiology, glycosynthesis, glycochemistry, and glycoimmunology. In 3 years, the Aviceda team has taken the invention from discovery to clinical development at an unprecedented pace.

“At Aviceda, we have assembled a world-class team of executives, scientists and scientific advisors to develop next-generation therapeutics harnessing the power of glycobiology to treat multiple diverse diseases with the common factor of needing immunologic modulation,” says Mohamed Genead MBA, MD, CEO and Co-Founder Aviceda Therapeutics Inc. & Aviceda Glycotech.