In a recent interview with PharmaShots, Dr. H. Michael Shepard CEO and Co-Founder of Enosi shared his views on the announcement that Enosi Life Sciences has filed a patent for three of its TNF-inhibiting molecules: EN1001 for autoimmune disease, along with EN2001 and EN3001 for autoimmune disease and cancer.

Shots:

• Enosi will offer use in multiple diseases and continue to address the market need for TNF-inhibitor therapeutics. EN1001: An enhancement to existing TNF-blocking technologies, this molecule only blocks Tumor Necrosis Factor Receptor-1 (TNFR1), instead of both TNFR1 and TNFR2
• EN2001: A growth factor trap that offers a completely different option for the treatment of rheumatoid arthritis, which can be combined with other RA therapeutics without fear of increasing immunosuppression
• EN3001: A molecule that will counter activation of TNFR2 as a bad actor in cancer and fibrotic diseases, offering a checkpoint inhibitor by increasing immunity

Tuba: What inspired you to form the new company focusing on autoimmune diseases and cancer?

Michael: My colleague Sir Marc Feldmann and I have both spent over 20+ years developing therapeutics, earning accolades such as the Laskar award within our respective fields of autoimmune disease and cancer. We came to the realization that there are certain commonalities between the two and an opportunity to address both through more precise targeting of inflammation and anti-tumor necrosis factor (TNF) receptors. The therapeutic candidates we're exploring would have the ability to be useful for a combination of multiple disorders, which increases their value and lowers the probability of failure. Our goal is to create more effective therapeutic solutions that offer lower toxicity, improved patient outcomes, and profitability for investors.

Tuba: How did the past experience of the co-founders aid in forming the company that brings two fields together?

Michael: Autoimmune diseases, like rheumatoid arthritis (RA), and cancer have many properties in common. These include inflammation, abnormal cell growth, and many of the same disease-associated immune cells. The obvious clinical similarity is that chemotherapy is used to treat both diseases. Shepard and Feldmann believe that by combining their knowledge in these two areas Enosi will discover new ways to treat each disease and some therapies that will be useful for both diseases. Since new drugs costs at least $150M to be developed and approved, this would represent an enormous saving to the healthcare system.

Evidence that this approach might work is that Shepard has discovered therapies that are successful at blocking tumor growth in mice. In collaboration, he worked with Feldmann, and together they showed that the new molecule, called a growth factor trap, also worked in mouse models of RA. Further work showed that it worked because many of the same growth factors at work in cancer are the same as those at work in autoimmune disease.

Tuba: Would you like to talk a little more about seed funding?

Michael: Venture Capital firms who put money into start-up companies gain a big benefit once the company has proven that its technology has a good chance to be successful in the clinic. This part of the drug discovery process does not take many millions of dollars. Enosi has decided to pursue seed funding from individual investors who will then benefit from this 'bump' in valuation. Enosi will subsequently be able to obtain much better terms when seeking funding from other sources. The initial investors will retain more ownership and benefit more from the increasing value of the company. This is not the usual way biotech companies are started. Enosi is a pioneer in the public funding of biotechnology.

Tuba: Can we have a glimpse of Enosi's pipeline of products?

Michael: It is very important for start-up biotech companies to focus on proving that they can be successful in creating their first product. However, the long-term health of the company requires long term planning where the goals are aligned with the know-how and resources of the company.

Enosi is focused on the EN1001 project.  EN1001 is a new kind of TNF Blocker (blocks induction of the inflammation of RA which is induced by the hormone called TNF). Current TNF Blockers are not prescribed for early disease, and often not for older patients, because of their side effects. The most important and frequent of these is an infection by tuberculosis, Listeria, Legionella, and Salmonella. Cancer in children and adults, and cardiovascular events (stroke) are also listed as important safety threats in the FDA 'black box' warning that is in every package of TNF Blocker (examples are Humira, Enbrel, Remicade). Nonetheless, medicines that block TNF are worth in the range of $40-50B per year. The biggest selling drug class in history. Enosi has discovered EN1001 Blocker to accomplish therapy of autoimmune disease. The company believes EN1001 will not have these side effects. It may then be given earlier in therapy, and thus could be curative, and it will be safer for children and older people.

There is another dimension to TNFR1. Recent science has indicated that persistent inflammation, caused in many cases by TNF and TNFR1, is associated with cognitive decline and Alzheimer's disease. This link has been proven in animal models, and in surveys of autoimmune disease patients treated with TNF Blockers, or not. It is unlikely that the current generation of TNF Blockers could be used for this purpose because of the side effects. However, EN1001 could potentially be used.

Tuba: How are these molecules different from the available TNF blockers and JAK inhibitors?

Michael: The current approved 'biologic' drugs to treat RA (Humira, Enbrel, Remicade) all are based upon TNF, either directly or indirectly. The TNF Blockers all 'trap' TNF and prevent it from activating inflammation. Unfortunately, these current drugs inhibit both of the routes that TNF influences the cell. The first route is called TNF receptor 1 (TNFR1). Stimulating TNFR1 causes inflammation. But there is a second receptor, called TNF receptor 2 (TNFR2). This second receptor is naturally supposed to turn down TNFR1. Unfortunately, the current TNF Blockers inhibit both receptors: TNFR1, the inflammatory or 'bad' receptor, and TNFR2, the anti-inflammatory or 'good' receptor. Blockage of TNFR2 also causes increased susceptibility to infection. Enosi's drug (EN1001) only blocks TNFR1 and leaves the anti-inflammatory TNFR2 alone.

When TNF activates TNFR1 it also activates many other inflammatory signals inside the cell, including JAK. Thus, inhibiting JAK cannot block all the different signals induced by TNFR1. This means that blocking JAK will only partially treat TNF-associated disease. Unfortunately, despite the fact that inhibiting JAK does work to slow down arthritis, it also has the same black box warnings as the TNF Blockers.

Tuba: Can we expect more programs from Enosi LifeScience?

Michael: Enosi also has three other programs that are all patented and could be useful in both cancer and autoimmune disease.

Tuba: Will Enosi develop these molecules on their own or look for a collaboration to develop them?

Michael: Enosi plans to take their molecules from discovery through early clinical trials to show that they work in patients. We will collaborate with academic institutions to help keep costs down, and we will collaborate with other biotech and pharma companies to help fund our projects.

Tuba: What are your expectations with the patented programs? How will it help in the growth of the company?

Michael: Enosi's intellectual property protects all of our programs and is meant to keep other companies from copying what we have done. We will always be willing to discuss a collaboration with another company if it increases the value to our shareholders.

Tuba: Do you think the molecules will be eligible for FTD, ODD, or BTD from regulatory bodies in the future?

Michael: ODD: Rare diseases are often a means to get faster drug approval, and to obtain funding from the FDA. It is possible that we may find an indication of this sort, but at the present time, we are focused on the big indications like RA and Crohn's Disease.

Tuba: As Enosi is looking for investors, whom can one contact to invest in the company?

Michael: You can check out our investor website: https://dealmaker.tech/invitations/enosi-regd/view or you can reach out to us directly:

Image Source: ABC News

About Author:

Dr. H Michael Shepard is a serial entrepreneur and also serves as Chief Executive Officer, Chief Scientific Officer, Co-founder and Board Member of Enosi Life Sciences. He led the research at Genentech that resulted in Herceptin/trastuzumab, an antibody therapy now used for HER2-positive breast and gastric cancers.

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