Nuvig Therapeutics is Rethinking the Standard of Care for Autoimmune Diseases with Novel Therapies

Intravenous immunoglobulin (IVIG) therapy is a common treatment for patients who have chronic or serious autoimmune diseases. The therapy is derived from donated plasma, where antibodies and immunoglobins are extracted from blood and later administered to patients who cannot produce the needed antibodies for a functioning immune system on their own. Intravenous immunoglobulin therapy is expensive—costing an average of $10,000 per dose and some patients can incur more than $100,000 in medical bills a year. Pamela Conley, Ph.D., co-founder and chief scientific officer at Nuvig Therapeutics, says a new alternative for patients who have autoimmune disease is long overdue, and her company is developing a novel immunomodulatory therapy which could possibly save patients both time and money.

Nuvig Therapeutics says its mission is to reimagine the therapeutic potential of recombinant Fc Ab fragments for autoimmune diseases without the use of any immunosuppressants. Its lead molecule, NVG-2089, recently underwent its first-in-human dosing and is on its way to enter a Phase 2 study as a possible treatment for Chronic Idiopathic Demyelinating Polyneuropathy (CIDP), a condition where people gradually lose the ability to walk and have numbness in their extremities. The company also plans to test the lead molecule in one or two different dermatological autoimmune disorders where IVIG use is validated as well. Pamela, who has more than 30 years of experience in the biotech industry, co-founded the company in 2021 based on research from Dr. Jeff Ravetch’s lab at The Rockefeller University in New York, which she worked on while vice president of biology at Portola Pharmaceuticals. “We brought that technology into Nuvig and expanded on it and improved the molecule,” she says. Shortly after emerging from stealth mode, Nuvig raised $47 million in Series A funding.

In this month’s Member Spotlight, we talked with Pamela about the need for innovation in the immunotherapy space and why it’s important for women in life science, especially at the C-level, to mentor fellow women in the field.

You received a Ph.D. in biochemistry at UC Berkeley and completed post-doctoral research at Stanford. How did you first get your start in the life science industry? Did you always know that you wanted to be a scientist?

I’ve been interested in biological sciences from an early age. The key moment for me was in high school, I had two wonderful chemistry teachers (one was a woman). They both encouraged me to pursue science further. I loved biology and chemistry, and when I went to college, biochemistry was a degree that was a nice mesh of the two—it allowed you to study the biological and chemical processes that affect human health. After college, I considered getting a Ph.D. or going to medical school. I loved the research aspect of it, so I decided to pursue my Ph.D. I think it was the right decision for me because it allowed me to translate my knowledge in the drug development space and be able to work with a team to then get drugs, that are novel therapies, to patients.

Did you ever envision or imagine at that time you would co-found a biotech company?

No! [laughs]. While I was in grad school was when the biotech industry in the Bay Area was just beginning—there was Chiron, Genentech and a few companies. After finishing my Ph.D., some of my colleagues and friends were going to work for biotech companies and it was appealing—it was something new. It was an exciting time in the Bay Area then.

Can you provide an overview of Nuvig’s approach on rebalancing immune function for chronic inflammatory and autoimmune diseases without relying on traditional immune-suppressive methods?

A lot of current therapies for autoimmune diseases are immunosuppressive. As examples, things like steroids, or even very well accepted drugs like Rituxan—which is a wonderful drug for cancer—work by wiping out some aspect of your immune system. Rituxan reduces your number of B cells and that’s a good thing for cancer. However, reducing B cell numbers in patients with autoimmune disease may leave patients susceptible to infections. The same thing is true for certain therapies for autoimmune diseases that target T-cells. If you cripple your T-cells, you can’t respond well to an infection.

Our approach is to exploit an aspect of our endogenous homeostatic mechanisms for maintaining balance among our immune system. Our immune system needs to be able to respond to a foreign antigen, virus or a bacteria, but you also need a way to turn that response off—otherwise we’d all be in an inflammatory state all the time.

One of the ways that our body turns that response off and rebalances things is to modify our circulating antibodies. Intravenous immunoglobulin (IVIG) shuts down these dysregulated immune responses in autoimmune diseases.

The problem with IVIG as a chronic therapy is you have to give really high doses—we’re talking one or two grams per kilogram of body weight—and patients have to sit in an infusion chair for six to 10 hours, and maybe a couple of days in a row, to get a full dose of the drug. Our molecule, NVG-2089, has distilled down the anti-inflammatory activity of IVIG and is 10- to 20-fold more potent. So instead of taking a six-to-10-hour infusion over a couple of days, you can get a one-hour infusion of our molecule and get the same benefit. We’ve shown that pre-clinically in a variety of different animal models of autoimmune disease.

Why the focus on treating CIDP and dermatology-related autoimmune diseases at this time?

The standard of care for CIDP is IVIG. But as we just said, it’s a hard therapy for many people to tolerate especially on a long-term basis. If you have to get it every three weeks, which is what many patients do, it’s very disruptive to your life.

We recently had a patient advisory board and heard first-hand how hard it is for them. CIDP usually appears in your thirties, forties or fifties, then you have to get treatments for the rest of your life. It’s also hard to diagnose because it can be confused with multiple sclerosis, myasthenia gravis or other neuromuscular diseases. Some of these patients have been on IVIG for 10, 15 years. They have ports implanted because it’s hard to find a vein to get the infusion. We believe our drug will be better than IVIG. These patients are clearly ready for something that’s a more tolerable therapy.

In addition, there are multiple dermatologic autoimmune diseases where there is still a huge unmet need. These diseases are commonly treated with corticosteroids, which do not always work very well and also have unwanted side effects for patients. With our improved safety profile, our drug could be a very attractive option in disease areas where corticosteroids are still commonly used today.

How does your new therapy offer a more potentially affordable alternative to IVIG?

With IVIG, there’s limitations to supply. You can imagine how it was during COVID, when nobody was donating plasma and not as much IVIG could be made. One advantage of our product is we make it recombinant using CHO cells—which is a common way to manufacture antibodies—so it’s not donor-dependent. Our cost of goods will be certainly very comparable, or potentially better, than that of IVIG as we won’t be supply-limited. We can make as much as we need.

NVG-2089 will soon be entering Phase 2. Is there additional exciting company news that you’d like to share?

We’re developing a pipeline that takes the same concept of what we’ve incorporated in our lead molecule and extending that to combining it with full-length antibody targets so that we can combine our mechanism with other validated mechanisms in autoimmune disease. We’re just starting to do that work. We have some preliminary results that are quite intriguing, and that could represent interesting partnering opportunities for us down the road with companies that have these antibody targets as therapies already—it might be a way to improve the efficacy of these existing molecules. That’s something we want to be able to focus on a bit more in the short-term now that we’re progressing into the clinic and into patients with our lead molecule.

What is your biggest challenge right now?

We face the same challenges as other small companies. We started in the end of 2021 with three people and we’ve grown to about 20. But in small companies, we all wear multiple hats. We also must be flexible and pivot quickly, depending on changes in the market and clinical space. We’re fortunate to have a really strong team—many of these folks I’ve worked with in the past and at other companies. As we’ve grown, we’ve been able to attract great talent. We always face the challenges of putting our funds to good use, advancing our molecules and hitting our timelines in a way that will allow us to continue to be able to progress these programs.

Recent stats show women make up only 23% of biotech CEOs. This number also applies to CSOs and only one in 4 biotech startups in the U.S. has a female founder. What is one thing you would like to see the life science industry do to increase the number of women at the C-Suite and on boards?

There must be a conscientious effort by investors and board members to encourage that. While there’s been an increase in those numbers, fortunately, we need role models for women in biotech at all levels.

It’s been interesting for me as a founding CEO, I have met other women CEOs in biotech, and there are quite a few now which is great. These CEOs embrace mentoring responsibilities and take that very seriously. There’s a lot of great organizations that are women-run, as well as women-focused networking groups and they’re very collegial, such as the Bay Area chapter of Women in Bio—they have bi-monthly networking happy hours. I think it’s getting better, but we need more of those role models for women, at the C-suite and across the board. We need to continue this mentorship through networking and continue to have more women becoming available for these roles and considered for these roles.

What piece of advice do you have for young people who wants to join the life science industry today, especially young women?

I think it’s probably one of the most exciting and rapidly changing types of careers that you could pick. If you like science, whether it’s biology, chemistry or even engineering, there’s overlap with all of the STEM functions to be able to contribute to companies in the life science space.

I’ve always been one of these people that believe you should love what you do and pursue it—work hard at it, educate yourself. It’s one of the more rewarding careers because you can see the impact of your work, and your team’s work and your company’s work, on patients. Your work is another way to benefit patients with chronic diseases, life-threatening diseases and genetic diseases.

As I reflect on my career as a scientist, I initially thought, ‘If I want to be a part of a biotech company, I have to work as a bench scientist.’ But as you work in a company, you realize you can branch off into a lot of other related areas—you can get involved in project management, regulatory affairs or in manufacturing—there’s just so many critical function areas that if you have a science knowledge base, you can diversify and do other things. You’re still contributing to that overall goal of getting drugs to patients and benefiting patients that way.