The Silicon Review
Platform technologies are known for having the ability to significantly improve the current product and generate a completely novel product. This, in turn, leads up to the opening of new avenues for drug development and discoveries, potentially increasing the therapeutic options for patients. Once a single therapeutic or compound is generated, and it progresses to show clinical benefit in patients, it is more likely that this platform can be used in other therapeutic areas too, thus derisking the future products and compounds. Despite the expensive initial upfront costs, platform technologies are known to provide a pragmatic solution for the challenges in production, while yielding more effective and safer therapeutic products.
Aviceda Therapeutics is a pre-clinical stage biotech company focused on the next generation of glyco-immune therapeutics utilizing the Glyco-Code technology to address the innate immune system and chronic non-resolving inflammation. The company was founded in 2018, and it is based in Cambridge, Massachusetts. Aviceda Therapeutics is developing nanoparticle therapeutics that can positively or negatively modulate any inflammatory cell. The nanoparticles are coated with and present glycan ligands designed and manufactured to bind with high affinity to a family of glycan binding self-associated pattern recognition receptors called Siglecs. These high-affinity optimized ligands on the nanoparticle can either agonize Siglecs, resulting in resolution of inflammation, or antagonize Siglecs to behave as a checkpoint inhibitor, for instance in the treatment of cancers. Aviceda has a lead nanoparticle therapeutic that can resolve both humeral and cellular innate immune activation in geographic atrophy secondary to age-related macular degeneration; it also has potential applications for treating loss of liver and lung function in Liver/Lung fibrosis. Aviceda’s pipeline also has inhibitors of Siglecs, which can treat cancers that evade immune surveillance by agonizing immune checkpoints.
In conversation with Mohamed A. Genead, MD, Founder, CEO and Chairman of Board of Aviceda Therapeutics
Q. How did you develop your glyco-immune therapeutics?
Glyco-immune therapeutics arose from the basic question of how immune cells differentiate between a healthy host cell versus a damaged host cell (cancer, oxidized cells) or a pathogen. Our scientific advisors and team helped launch the whole field of glycoimmunology with the discovery that certain glycans ligands (self-associated molecular patterns) found on the surface of cells bind to a family of self-associated pattern recognition receptors called Siglecs; that these receptors are found on all immune cells; and that his binding activity can either shutdown or prevent inflammatory/immunological activity. Our team then pioneered the use of a high-throughput glyco-ligand screening method to identify targets and developed a glycan presenting nanoparticle platform. Combined with Aviceda’s experienced drug development team, these advancements launched the field of glyco-immune therapeutics.
Q. What are the major illnesses that can be addressed by your therapeutics?
Aviceda’s therapeutic platform’s strength is its ability to address diseases that require profound immune downregulation and diseases that evade immune surveillance and require immune normalization. Aviceda’s scientific platform and its technology can resolve acute or chronic non-resolving inflammation in diseases, which include several ocular diseases (age-related macular degeneration, diabetic retinopathy, retinal fibrosis, ocular tumor, and allergic/inflammatory ocular diseases such as dry eye and allergic conjunctivitis) and systemic diseases with significant unmet medical needs such as fibrotic diseases (idiopathic pulmonary and liver fibrosis). Aviceda’s therapeutics can also block immune evasion in diseases like cancer and neuro-inflammatory and degenerative diseases, including Alzheimer’s disease, infectious diseases (anti-viral “HIV”), and autoimmune diseases.
Several of these conditions have no current treatment modalities or are managed by therapies intended only to slow progression but not stop or reverse the pathology. Because Aviceda therapeutics resolves inflammation or normalizes immune surveillance by profoundly and specifically modulating the immune system’s inherent self-recognition mechanism, patients treated with this technology will be immune normalized, not immunocompromised or pathologically inflamed. Furthermore, the resolution of inflammation versus the blocking of activators of inflammation can potentially reverse pathology.
Q. What are the risks involved in glyco-immune therapeutics, and how do you address them?
The risk involved in glyco-immune therapeutics is that the clinical effect will not reflect current immune or anti-inflammatory therapies. Resolution of inflammation may not be accompanied by immune compromise, and restoration of immune surveillance may not be accompanied by non-specific inflammation. Because Aviceda is using naturally occurring glycans, acute dose-limiting toxicity may not be found, and the lack of theoretical toxicity will pose a risk in drug development. To address this potential lack of clinical toxicity, we will need to determine the maximum dose empirically and educate the clinical trial community on the potential for no clinical toxicities.
Q. There is a concern right now, that immunotherapy works for less than half the people who try it. Is this true? Explain.
Classical immunotherapies block specific pathways in the inflammatory cascade, leaving other non-targeted escape pathways functional to propagate inflammation. These escape pathways result in a smaller responder population. Agonizing a Siglec on an immune cell profoundly shuts down all immune-activating pathways specifically within that inflammatory cell. Theoretically, this should translate into a larger population of responders.
In the field of immune-oncology, the programmed cell death protein 1 (PD-1), is the predominant target for the dominant immunotherapeutic class called checkpoint inhibitors. Current cancer checkpoint inhibitors are effective in fewer than 50% of patients, as stated in this question. While immune checkpoints (PD-1) utilize an intracellular inhibitory motif (ITIM) that can shut down the activation of an immune cell, PD-1 is only found on T-cells. Siglecs, Aviceda’s target biology, represents the largest family of receptors that utilizes this inhibitory motif (ITIM).
Several properties differentiate Siglec receptors from the PD-1 receptor. First, all Siglec receptors bind and are agonized/antagonized by glycans, not proteins like the PD-1 Ligand. Second, several receptors in this family carry an ITIM (the same inhibitory motif as PD-1) but are found on different immune cells. In fact, every class of immune cells (T-cells, B-cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, dendritic cells, and monocytes) have glycan recognizing inhibitory Siglecs.
Third, developing high-affinity antibodies to block siglec receptors is difficult compared to protein receptors, but yields an exponentially higher-affinity binding agonist/antagonist. Furthermore, Aviceda’s proprietary high-throughput ligand screening allows the design and identification of glycan ligands that are either high-affinity specific to a single Siglec receptor or high-affinity specific to multiple Siglecs (Pan Siglecs).
Fourth, because glycan ligands can be designed to be pan-specific or combined into a cocktail of multiple single siglec specific ligands, a single pharmaceutical product can inhibit several siglec receptors and subsequently shut down multiple activation pathways in several inflammatory cells. The ability to inhibit multiple checkpoints receptors in different cells with one therapeutic should theoretically increase the responder population to greater than 50%.
Q. How are you planning to continue development of the Glyco-code technology platform?
Aviceda is establishing the plausibility of sialic acid-targeting via nanoparticle mimicry in specific disease states, with the acknowledgment that this mechanism has relevance for a broad range of diseases associated with an inappropriate immune activity or immune cell deactivation. Our lead candidate (AVD-104) targets age-related macular degeneration (AMD). We have already developed pre-clinical assets for cancer, fibrosis, neurodegeneration, and other areas of medicine.
Meet the leaders behind the success of Aviceda Therapeutics
Mohamed A. Genead, MD (Founder, Chairman of Board & Chief Executive Officer), a serial life-sciences entrepreneur, senior innovative biopharma executive, physician-scientist, and inventor with 20 plus years’ experience in pharmaceutical drug & business development and corporate strategies execution from discovery to late development and commercial phases. Co-founder of several start-up/biotechs and being instrumental in the raising of over $500M in venture and institutional capital for numerous life-sciences biotech companies. A board member of several ophthalmic organizations and scientific advisory boards.
Prof. Chris Scott, Ph.D. (Scientific Co-Founder): Professor Scott is Director of the Centre for Cancer Research and Cell Biology at Queen’s University Belfast. Following a primary degree in Biochemistry, he undertook a Ph. D. and post-doctoral training at Queen’s in molecular enzymology. In 2001, Chris was one of the founding members of QUB spinout company Fusion Antibodies Ltd., before returning to Queen’s in 2003 to take up an academic position. Professor Scott is internationally renowned for his work in the development of antibody and nanomedicine-based therapies for the treatment of cancer and other conditions.
Derek Kunimoto, MD (Co-founder), a top-tier retina key opinion leader in Ophthalmology. A recipient of the Rhodes scholarship, where he received a JD from Oxford University. Business & Corporate Strategy background at Mckinsey & Company. Plays an instrumental role in the approval of many ophthalmic therapeutics as a principal investigator. He developed one of the largest retina practices and clinical trial programs in the US.
Michael Tolentino, MD (Co-founder), an ophthalmologist and life-sciences entrepreneur with significant scientific contributions to the ocular angiogenesis field for macular degeneration and siRNA therapeutics. The inventor of Bevasiranib and a co-founder of Acuity Pharmaceuticals, which merged to become OPKO Health after taking the first siRNA therapeutic to a Phase III clinical trial.