ILC Therapeutics' Interferon Alpha 14 Joins The COVID-19 Fight

By Matthew Pillar, Editor, Bioprocess Online

The Glasgow-based emerging biopharma is progressing on two therapeutic candidates, an rIFN alpha14 focused on early-stage COVID-19 infection and a tick-derived Evasin targeting late-stage COVID-19 ARDS patients.

Veteran biotech CEO Dr. Alan Walker recently signed on with ILC Therapeutics to lead the company’s multi-pronged foray into the COVID-19 battle. It’s not a “me-too” moment for the company. “We didn’t go looking for COVID-19 therapeutics, COVID-19 came looking for us,” he says.

Founded in 2012, ILC is an early stage biotechnology company focused on modulating the Innate Immune System through the development of novel peptide therapeutics for the treatment of Cancer, Atopic Dermatitis and Psoriasis. When the company saw that COVID-19 ARDS (Acute Respiratory Distress Syndrome) was an inflammatory disorder involving innate immune cells like Natural Killer (NK) and Neutrophils, it began to investigate applying its recombinant Alpha 14 interferon (rIFN alpha14) to the treatment of COVID-19 ARDS.

Dr. Walker explains that the indication and its potential treatment are not uncharted territory for ILC Therapeutics founder, Professor Bill Stimson. Stimson was involved in the use of the first human mAbs for cancer therapy, and he had extensively researched multi-subtype alpha interferons to treat SARS in 2005. As a result, Professor Stimson had identified Alpha 14 as the most potent alpha interferon to treat SARS, a close relative of COVID-19. “We already had data showing it was antiviral,” says Dr, Walker. “The new data we have showing its effects on reducing Cytokine Storm, up regulating viral killing NK cells and downregulating lung damaging Neutrophils made this molecule an ideal candidate for examination in COVID-19 ARDS.”  The company is now in the process of testing its rAlpha 14 against COVID-19 strains grown in a laboratory, and it hopes to be able to test against patient blood and possibly lung lavages in the near future.

ILC Therapeutics currently produces research grade, 98 percent purity rAlpha 14 using E.coli with very high expression. “We plan to have established a Master Working Cell Bank and transferred our upstream and down stream production process to a leading European CMO by the end of 2020,” says Dr. Walker.

A Late-Stage COVID-19 Therapy From An Unlikely Source

ILC Therapeutics’ Alpha 14 interferon candidate has the potential to treat COVID-19 before the onset of ARDS, the company is also working with Professor Shoumo Bhattacharya at the University of Oxford to develop a therapy—derived from an unlikely source—for treatment of late-stage progression of the disease. ILC and Professor Bhattacharya are working on therapeutic Evasins, which are molecules derived from ticks. Ticks produce Evasin molecules to prevent blood clotting and immune reactions when they are feeding from their hosts. They’re responsible for the tick’s ability to burrow into its host undetected. But rest assured, the company isn’t farming ticks to feed Evasin supply. “We’re not isolating Evasins from ticks, and no volunteers are required,” explains Dr. Walker. “Rather, the sequence of the Evasins, with some very clever modifications by Professor Bhattacharya, have been expressed in a suitable microbial expression vehicle. We are optimizing expression at the moment, but our next step would be to create a Master Working Cell Bank for cGMP production. The high purity of our research grade material allows us to progress in vitro and pre-clinical work very quickly,” he says.

While the Alpha 14 Interferon is a messenger molecule that mediates many beneficial effects by binding to Interferon receptors on almost every healthy cell in the body, Dr. Walker explains that Evasins work very differently. “Evasins bind to other chemical messengers and activators, stopping them from delivering their signals,” he says. “Interferons probably work best before Acute ARDS has started in patients, but Evasins could work even in the extreme conditions of advanced ARDS by putting out the chemokine and cytokine fire that is destroying lung tissue like a fire extinguisher.” Sadly, in keeping with the fire extinguisher analogy, Evasins will not repair damage already done to the lungs , but Dr. Walker contends that they may prevent further damage and allow the retention of enough lung function and alveolar integrity to enable oxygen uptake.

Fruitful Funding Prospects For COVID-19 And Beyond

Dr. Walker says that in addition to its potential to treat COVID-19, the Alpha 14 Interferon has the potential for use in the treatment of several other disease states where innate lung inflammatory responses are out of control, such as viral respiratory diseases and allergic asthma. This multi-indication scenario, he says, bodes well for the emerging company’s funding prospects. “Although our immediate fund-raising focuses on COVID-19, we expect long term revenues to be generated from all of these indications,” he says. “The safety studies we perform should be applicable to all these applications, and we expect to extend the approved revenue generating indications beyond COVID-19 ARDS after licensing.” The company is currently working on securing the funding necessary to take its candidate through completion of a small Phase 2a study using COVID-19 patients. “Gurus like Bill Gates pointed out in 2015 that such a pandemic was inevitable, and certainly will occur again with new pathogens,” says Dr. Walker. “Treatments that are likely to cover a wide spectrum of such threats have long term value”

Acknowledging the cooperative therapy development landscape COVID-19 has spawned, Dr. Walker calls it unprecedented. “It’s a great response to the threat to our society,” he says, while also being quick to point out his company’s differentiators. “Unlike many companies jumping on the COVID-19 bandwagon, our research focus has not substantially changed from investigating ways of controlling innate immune inflammatory responses,” he says. “The in vitro data we discussed earlier showing our ability to control the key cells implicated in COVID-19, NK cells and Neutrophils was already in our patents.” ILC Therapeutic’ data on controlling IL-6, IL-17, IL-8 and other cytokines and chemokines that create deadly “Cytokine Storms” in COVD-ARDS patients was also already in its patents. “Some of the most intractable problems in medicine today are directly linked to the Innate Immune System, and that is why we have spent years in this area.”

Looking To History To Guide The Path Forward

Moving forward, Dr. Walker predicts that the COVID-19 pandemic will propel greater focus on therapies that leverage the Innate Immune System. “The Innate Immune has been ignored in favor of the Adaptive Immune System, but it is a vital part of our immune defense system.  I would envisage that Alpha 14 and Evasins and their ability to control inflammatory responses could be widely used in many areas of Respiratory Medicine long after COVID-19 has become a part of history,” he says. “Our Chairman, Dr. Magnus Nicolson, recently told me that the search for COVID-19 treatments was a bit like the Space Race in the 1960’s. He suggested that the global focus on COVID-19 will transform respiratory medicine in the same way, and that far more patient lives will be saved by the advances we are making in this area today than will be lost to COVID-19.”

Learn more about ILC Therapeutics and its approach to COVID-19.