Expanding Therapeutic Focus

Improving quality of life

In addition to heavily studied areas like neurology and oncology, the scope of companies developing therapeutics that target unmet medical needs has widened dramatically in recent years. Indications that have been without effective treatments for decades are now gaining renewed attention, while others with a well-entrenched standard of care have companies seeking to redefine treatment paradigms, in some cases even offering cures. This is happening across single-gene disorders, such as cystic fibrosis or Huntington’s disease, as well as common polygenic diseases, such as diabetes and heart disease. Researchers are making remarkable progress in targeting the underlying genetic basis of disease rather than symptomatic relief. The resulting therapeutic gains are awe-inspiring, and a slew of drugs are being developed to benefit patients.

One of the most obvious areas of need is in the autoimmune disease space. Psoriasis and ulcerative colitis are just a few diseases in this area with large addressable markets. For context, AbbVie’s Humira brought in US$19.83 billion in revenue in 2020. Furthermore, it is anticipated that this market will continue to grow as countries become more industrialized. This has led to a “hygiene hypothesis” which suggests that, as we evolve into a cleaner society that is less exposed to things humans were exposed to historically, we are not challenging the immune system as much anymore, ultimately leading to more autoimmune disease.


“COVID-19 has exposed that baseline health is critical to manifestations of the virus. From an investor standpoint, metabolic diseases represent a high bar due to there being such a complex polygenic and environmental interaction, and cardio-metabolic diseases have been deemphasized in the investment community. COVID-19 has brought back the importance of obesity as it puts one at high risk. I hope that in the near future there will be renewed interest from investors in chronic disease because of its interplay with acute viral infections.”

Joyce Harper, CEO, Ferox Therapeutics

The autoimmune indication market is expected to be worth US$153 billion by 2025, and companies like Blacksburg-based Landos Biopharma could be poised to benefit immensely. Landos CEO, Dr. Josep Bassaganya-Riera, underlined that the company’s initial autoimmune indication focus was on Crohn’s disease and ulcerative colitis (UC), two diseases with an extremely large unmet medical need and a multi-million dollar market. “The way we are approaching autoimmune diseases is by focusing on targets at the intersection of immunity and metabolism. We are leveraging our AI-based integrated computational platform to identify important new molecular targets,” he said.

Another player with a drug addressing UC is Arena Pharmaceuticals, which this February completed full enrollment of its Phase 3 ELEVATE UC 52 trial evaluating the safety and efficacy of Etrasimod. “There are 150,000 moderate ulcerative colitis patients in the US that have ongoing active disease and are currently treated by older agents like 5-ASA and pulse steroids. These are prime candidates for receiving a once a day oral that has the profile of Etrasimod,” Amit Munshi, president and CEO of Arena, commented.

One of the most welcome arrivals to the autoimmune field has been Vedanta Biosciences, a Founded Entity out of PureTech Heath, which recently received a US$25 million investment, as part of the Pfizer Breakthrough Growth Initiative. The funds will help Vedanta advance their Phase II study of VE202 in inflammatory bowel disease (IBD). According to CEO, Bernat Olle: “We decided to focus on how microbes in the intestine shape immune responses, and from a modality point of view, we focused on using defined consortia of bacteria.”

When comparing VE202 with Seres Therapeutics highly anticipated SER-287, Olle explained: “VE202 is a standardized product. There is no donor step in VE202. We start from clonal cell banks of bacteria that are sitting in a freezer, which we then expand by fermentation to create a product that is always going to have the exact same composition, potency and dose.”


Vedanta’s platform also allows it to address scalability issues common in the field, because they produce the drug by fermentation, enabling them to scale up production to make as needed at a much lower cost of goods than a donor-derived procedure. Olle’s ambitious agenda is fueled by a belief that microbiome therapeutics will see major breakthroughs that will fundamentally change the biotech industry in the coming years. “Our ultimate vision is to enable defined consortia of bacteria as a new drug modality, in the same way that Genentech enabled protein biologics and Alnylam enabled RNAi therapies as new modalities,” he proclaimed.

In the realm of dermatology, Novan, whose proprietary nitric oxide technology came out of the University of North Carolina Chapel Hill in 2008, is also leveraging its platform with anti-microbial and anti-inflammatory properties to address skin diseases with unmet needs. Its SB206 seeks to treat Molluscum patients, a highly contagious disease that can spread to become as many as 100 lesions on the body. The current standard of care is to let it resolve on its own for 13 months. However, Novan seeks to solve this in 12 weeks.

In explaining the company’s technology, Paula Brown Stafford, president and CEO said: “Nitric oxide is a heavily researched molecule, but there have been challenges associated with controlling the release of the gas and the ability to stabilize and store it. That is what Novan has been able to do with our NO Platform. We store nitric oxide on a polysiloxane backbone, using our proprietary Nitricil technology, and then we can tune the timing and duration of the NO release via our formulation science.”


Another area of huge unmet need is in the field of ophthalmology. As it stands now, for the many diseases affecting the back of the retina, treatments are either nonexistent, or there is a significant population of non-responders to available therapies representing a large, underserved population. For example, dry age-related macular degeneration, which leads to irreversible blindness due to degeneration of the retina, has no available treatment and an estimated US patient population of nine to 10 million. For other retinal diseases, such Retinis Pigmentosa or Leber Congenital Amaurosis, there are no available treatments. This is why Ocugen, in addition to spending the past year developing a Whole-Virion Inactivated Vaccine for COVID-19 alongside Bharat Biotech (COVAXIN), has a program developed through its modifier gene therapy platform that targets nuclear hormone genes (NHRs), which regulate multiple functions within the retina. According to Ocugen’s CEO and co-founder Shankar Musunuri: “By targeting a functioning nuclear gene like a NR2E3, it upregulates all the functional networks associated gene expressions, resets homeostasis, and restores normal cell function.”

On account of this, Ocugen has received four orphan designations from FDA and orphan medicinal product designation for the treatment of both Retinitis Pigmentosa and Leber Congenital Amaurosis from the European Commission.

Rare and Orphan Disease

Until the Orphan Drug Act was authorized in 1983, many rare diseases remained unaddressed – in truth, orphaned by the industry due to complex biology, challenges with diagnosis, difficult patient identification, and other issues including navigating market access hurdles across multiple geographies. Thankfully, today things have progressed substantially. Specifically, in 2020, the FDA approved 32 novel drugs and biologics with orphan drug designation. “There has been an immense amount of advance as a result of the Orphan Drug Act… This act prompted industry to turn its attention toward these diseases, and NTM is one such disease which fits that description. It is common in that pathogens are ubiquitous in the environment, so we are all exposed to it, but only a very small group of people develop it into an indolent disease that requires treatment. It numbers around 100,000 patients in the US, of which we went after the most severe, the refractory population, which numbers between 12,000 and 17,000,” commented Insmed CEO, William H. Lewis, who is leading the charge to bring ARIKAYCE, the first ever approved therapy for the treatment of NTM to market. Lewis added: “The results have been gratifying because we saw almost a third of the patients with no evidence of infection after treatment with our drug in our phase three trial.”

Another important approval that came in 2020 in the orphan disease space is LFB USA’s Sevenfact. This product is indicated for Hemophilia A and B patients with inhibitors. It represents a relatively small market the company is treating. “Even though there is a substantial Hemophilia patient pool, once you go into the A&B patients with inhibitors, there are less than 1,000 patients in the US. It is a targeted market, with only one other product approved, and that product has held a monopoly position for many years. As a result, LFB had a very big incentive and was determined to bring an additional choice to these patients,” opined Jose Antonio Moreno Toscano, CEO of LFB USA.

Because patient pools in Rare and Orphan disease are small, patient advocacy groups can play an essential role in driving innovation, fundraising and with clinical trial development. For this reason, companies must cultivate close relationships with the patients they are attempting to serve. “You cannot run your communications for investors sake only. There are many companies that still try to do that; they become public, and they realize that they have obligations to their shareholders and that drives the communication. That way won’t scale long term. What you really need to do is build a foundation of key messaging and positioning aligned with key audience if you are in rare disease patient communities. All of that communication and relationship building builds up to creating value for the company,” explained Donna LaVoie, a strategic communications expert who leads LaVoieHealthScience.

“Development of a pharmaceutical product and getting FDA approval are important first steps. However, regulatory approval does not always equal commercial success. Commercial success, especially with products under orphan drug designation, is challenging. Your work with payors needs to be very targeted and clear.”

Jose Antonio Moreno Toscano, CEO, LFB USA

Cystic Fibrosis

Many CF patients experience symptoms involving the digestive system, which are often associated with the production of a thick mucus in the pancreas that blocks the release of the digestive enzymes needed to break down food. This deficiency in exocrine pancreatic enzymes, resulting in a patient’s inability to digest food properly, is referred to as EPI. To treat EPI, CF patients often need pancreatic enzyme replacement therapy (PERT), a treatment designed to supplement enzyme levels to the digestive system. Enzymes used in PERT are typically derived from pigs or other animals, prompting the development of alternative formulations not derived from animals. The active ingredient in AzurRx’s MS1819 is a synthetic enzyme derived from yeast cells, thereby avoiding the use of animal products. James Sapirstein, president and CEO of AzurRx BioPharma, reflected: “When I first started my career with Eli Lilly, we had a product derived from the recombinant DNA of E. coli called Humulin. The intent was to replace 85 years of porcine-derived insulin in diabetic patients. It took Lilly a few years, but human insulin eventually became the standard of care. We see our MS1819 yeast-derived recombinant lipase as analogous.”

The benefits of the AzurRx approach are that it does not have the same antigenicity issue as a porcine-derived product. The production process will also be safer, standardized and more consistent. “We are not depending on pig herds that sometimes get slaughtered because of swine flu or for some other reason. More importantly, MS1819 requires the ingestion of fewer capsules each day. As a pharmacist, compliance is key. The less medication required, the more compliant the patient will be,” Sapirstein expounded.

Progressing Behind the Scenes

It is important to recognize that while the dominant headlines of 2020 were about progress made across the industry with respect to COVID vaccine development, there was also much progress made in areas that for a long time have been completely neglected. It is a strength of the US healthcare system that there are private companies who willingly embrace enormous financial risk to bring drugs to market for small and large segments of the population. This has hugely beneficial implications for patients, and gives renewed hope to those who once thought they would never be cured.

Image courtesy of Landos Biopharma