Epoch 17: Fibrosis- From Basics to Breakthroughs

Approved Products, Competitive Intensity, Deal Comps

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Hello Avatar! Welcome back for another week of biotech analysis. Today is Sunday, which means this is our Building Biotech newsletter that is focused on discussing biopharma strategy topics. Today we are going to cover the field of fibrosis.  For many of you this may be a new topic.  The reason you do not hear so much about fibrosis is that it is a graveyard of drug development.  Translation of effective therapeutics has remained elusive.  However, there are a number of pan-fibrotic agents now in early to mid stage clinical development which have our attention.  Today you will learn about what fibrosis is, which companies play in the space, which mechanisms they target and what market caps and deal comps are historically associated with this class.

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FIBROSIS RENNICIANCE

If fibrosis is not on our radar yet as a disease with high unmet we suggest you simply follow the money. This week saw Endeavor BioMedicines announce a $132M Series C to advance ENV-101 taladegib in idiopathic pulmonary fibrosis (IPF).  

The magnitude of the raise is a signal that investors are ready to back clinical stage fibrosis.  The deal syndicate for Endeavor includes top investors such as, Matrix Capital, Fidelity, Invus, SymBiosis, Velosity, Woodline, Tekla, Ally Bridge, Avidity, Eckuity, Longitude, Omega, Perceptive, Piper Heartland, Silver Arch Bio, and T. Rowe Price Associates.  Clearly this one is ready to go public in the near future!

FIBROSIS OVERVIEW

Before digging down into the specifics we begin with some background on the disease itself. Those well versed in this space can feel free to skip ahead.

Fibrosis, responsible for a significant portion of global mortality and typically manifests itself when the body's natural healing mechanisms misfire. When the body sustains an injury, fibroblast cells rush to the site to facilitate repair. However, under certain circumstances, these fibroblasts can undergo a transformation into hyperactive myofibroblasts. Instead of completing the healing process and dissipating, these myofibroblasts initiate an overzealous healing response, leading to excessive scarring. This uncontrolled tissue remodeling characterizes fibrosis, which can occur in vital organs such as the lungs, heart, kidneys, and liver, posing severe health risks and often proving fatal.

Among the organs susceptible to fibrosis, the lungs stand out prominently. Comprising millions of delicate air sacs, any damage to the thin walls of these sacs can trigger a buildup of scar tissue, impairing oxygen diffusion into the bloodstream. Consequently, lung function deteriorates as the scar tissue stiffens the lungs, impeding their ability to expand and contract efficiently. Without intervention, such as a lung transplant, the prognosis for individuals suffering from severe pulmonary fibrosis can be dire, with compromised breathing leading to fatal consequences.

Liver fibrosis is a progressive condition characterized by the accumulation of scar tissue within the liver, often resulting from chronic inflammation and injury. One prominent cause of liver fibrosis is non-alcoholic fatty liver disease (NAFLD), particularly its more severe form known as non-alcoholic steatohepatitis (NASH). In NASH, the accumulation of fat in the liver triggers inflammation and oxidative stress, leading to the activation of hepatic stellate cells and subsequent deposition of collagen-rich scar tissue. As liver fibrosis advances, it can impair liver function and ultimately progress to cirrhosis, increasing the risk of liver failure, hepatocellular carcinoma, and mortality. Understanding the pathogenesis of liver fibrosis, particularly its association with NAFLD and NASH, is crucial for developing effective diagnostic and therapeutic strategies to mitigate the growing burden of liver-related morbidity and mortality worldwide.

Kidney fibrosis represents a significant challenge to treat and is characterized by the progressive accumulation of scar tissue within the renal parenchyma. This fibrotic remodeling often stems from various insults, including prolonged inflammation, ischemia-reperfusion injury, or chronic diseases such as diabetes and hypertension. As fibrotic tissue replaces functional nephrons, renal function declines, eventually leading to end-stage kidney disease (ESKD) necessitating renal replacement therapy such as dialysis or transplantation. Despite its clinical significance, therapeutic options for kidney fibrosis remain limited, primarily due to the complex interplay of molecular pathways involved in its pathogenesis. Developing effective therapeutics for kidney fibrosis poses considerable challenges, including the need to target multiple cellular and molecular mechanisms simultaneously while minimizing off-target effects. However, ongoing research efforts aimed at elucidating the underlying pathophysiology of kidney fibrosis offer hope for the development of novel therapeutic strategies to prevent or reverse fibrotic kidney disease and improve patient outcomes.

Similarly, cardiac fibrosis emerges as a consequence of heart muscle damage, often stemming from conditions like heart disease or heart attacks. As scar tissue infiltrates the heart muscle, it loses its elasticity and vigor, diminishing its capacity to pump blood effectively throughout the body. This decline in cardiac function precipitates heart failure, further illustrating the debilitating consequences of fibrotic conditions on vital organ systems. Despite the grave implications of fibrosis on human health, treatment options remain limited, with transplantation often emerging as the last resort for individuals grappling with end-stage fibrotic diseases.

A few months back the Stifel team did an excellent job laying out the case for fibrosis as an emerging area of therapeutic development. We will share highlights from their analysis overlaid with our own commentary which will cover an overview of approved products, market growth projections, the competitive landscape, and deal comps for licenses and acquisitions.