Pano Therapeutics, Inc. - Overview
Pano is a preclinical stage biotech company focused on the discovery and development of small molecules targeting cellular energetics - with the ultimate goal of extending healthy human lifespan, or ‘healthspan’. Pano’s drug candidates are partial inhibitors of Complex I of the mitochondrial respiratory chain and indirect modulators of pathways associated with cellular energetics such as AMPK and mTOR. Pano’s initial lead drug candidates are patented novel biguanide compounds that have been chosen for their selective activity across the range of organic cation transporters (OCTs) to enable a tissue-selective drug targeting approach. Pano is initially advancing preclinical lead drug candidates for rare / orphan and high prevalence chronic kidney diseases (CKDs) with significant unmet medical need, with an initial focus on Autosomal Dominant Polycystic kidney Disease (ADPKD).
Pano’s platform has been designed to discover additional novel biguanides and other classes of compounds optimized for both their inhibitory activity at mitochondrial Complex I and selective activity across OCTs for potency, selective tissue exposure, PK, and ADME. Pano believes that this approach can generate multiple drugs optimized for a range of therapeutic areas and disease states.
Below sections include:
- The Emerging Bioenergetic Paradigm
- Pano’s Biguanide Discovery Platform
- Pano’s Strategy and Business Model
- Pano’s Current Preclinical Development Programs
- Pano’s Intellectual Property
The Emerging Bioenergetic Paradigm
As life evolved from unicellular organisms over the past ~1.5 billion years, mitochondrial endosymbiosis enabled the evolution of multicellular life. As a result of this evolutionary connection to the basic eukaryotic cellular circuitry, mitochondria are intimately linked to many cellular and physiological functions, exert systemic effects upon various organ systems, and support the resilience of complex life. Consequently, once considered exclusively the ‘powerhouse of the cell’, mitochondria are now recognized to perform multiple essential functions beyond energy production, impacting most areas of cell biology and medicine – including the physiology of aging itself.
This emerging bioenergetic paradigm suggests that mitochondrial dysfunction contributes to the development of a broad range of diseases by altering complex cellular and physiological functions: energy metabolism, cellular signaling, oxidative stress, metabolic flexibility, as well as cell proliferation and death. Many environmental stressors and behavioral patterns, as well as genetic factors, can lead to mitochondrial dysfunction that may manifest in a constellation of acute and chronic diseases - including metabolic and fibrotic disorders, cancers, neurodegenerative & neuropsychiatric disorders, and cardiovascular disease, inter alia.
Pano believes that partial inhibition of mitochondrial Complex I and the consequent indirect modulation of pathways associated with cellular energetics, such as AMPK activation and mTOR inhibition, presents as an under-exploited therapeutic strategy with broad potential applications for drug development.
Pano’s Biguanide Discovery Platform
Pano believes that the principal mechanism of action that drives the broad therapeutic potential of biguanide drugs is the partial inhibition of mitochondrial Complex I and consequent indirect activation of AMPK and inhibition of mTOR. Modulation of these pathways results in inter-related benefits such as:
1. Breaking the connection between abnormal metabolism and associated diseases - intervention into pathways directly associated with the onset and progression of a range of disease states associated with mitochondrial dysfunction and metabolic dysregulation;
2. Enhancing metabolism and mitochondrial homeostasis - mediation of the cellular responses to energetic stress such as mitochondrial dynamics and quality control to promote mitochondrial homeostasis, function, health, and resilience.
Biguanides variably rely on Organic Cation Transporters (OCTs) to access cells and their engage with their mitochondrial target. These OCTs are themselves highly variable in their expression across different tissues and organs.
Metformin, a biguanide drug and one of the most prescribed drug worldwide, has been used for decades as the first-line treatment for type 2 diabetes. More recently, Metformin has been demonstrated to be an interesting prototype biguanide drug for numerous therapeutic applications, including the treatment of various cancers and degenerative disorders, inter alia. Notwithstanding Metformin’s prototypical prospects across therapeutic areas, there has been very limited success to date in its clinical development indications other than type 2 diabetes. Pano believes that Metformin’s therapeutic applications have been substantially limited by its low potency at its mitochondrial target, poor PK, and ADME dependence on OCTs resulting in inappropriate tissue distribution & exposure as well as safety concerns for select applications.
Pano has developed and implemented a platform for the discovery of biguanide drug candidates that have both:
1. Selective & enhanced activity across the full range of OCTs to enable tissue targeting & enrichment for a range of therapeutic and preventive applications;
2. Enhanced partial inhibition potency at mitochondrial Complex I.
Pano’s Strategy and Business Model
Pano’s R&D platform and business strategy are focused on the discovery and development of patented novel drug candidates that are partial inhibitors of mitochondrial Complex I and indirect activators of AMPK for a range of rare genetic as well as highly prevalent chronic diseases associated with mitochondrial dysfunction and/or metabolic dysregulation - initially OCT-optimized biguanides.
Pano’s R&D platform strategy currently comprises two main components:
1. Drug discovery and lead optimization to select biguanide drug candidates optimized for both their activity at mitochondrial Complex I as well as specific OCTs for selective tissue targeting / enrichment and optimization of PK & ADME;
2. Drug development of patented novel biguanide compounds for a range of therapeutic applications with an initial focus on chronic kidney diseases.
Pano’s Current Preclinical Development Programs
Pano believes that its platform strategy can generate multiple developmental assets for a range of therapeutic areas and indications for which partial Mitochondrial Complex I inhibition and AMPK activation have been shown to be prospective therapeutic strategies.
Pano has discovered and patented a novel series of highly OCT-selective biguanides from which lead candidates have been selected for preclinical drug development programs comprising rare/orphan and highly prevalent kidney diseases.
Pano’s initial focus indication is Autosomal Dominant Polycystic Kidney Disease (ADPKD) for which our initial lead candidate is in advanced IND-enabling studies, and we aim to file an IND in 2024. Other prospective rare kidney indications include Alport Syndrome, FSGS, Tuberous Sclerosis Complex, and; prospective high prevalence kidney indications include diabetic nephropathy, non-diabetic chronic kidney disease / kidney fibrosis, and renal cell carcinoma.
Pano has also demonstrated in vivo proofs of concept for its lead candidates in type 2 diabetes as well as select female reproductive cancers, demonstrating potential opportunities for both label expansion across cardio-renal-metabolic indications as well as adjacent therapeutic areas such as oncology.
Pano’s Intellectual Property
Pano’s IP portfolio comprises issued composition of matter patents specifying novel series of OCT-optimized biguanide compounds.
