By: Robert Mittendorff MD, Jason Grosz, and Jack Grimes
B Capital is proud to partner with Nuvig Therapeutics, a clinical-stage biotech company pioneering novel immunomodulatory therapies for autoimmune diseases. The company is advancing its lead program, NVG-2089, through clinical development, with significant potential to transform the treatment of conditions such as chronic inflammatory demyelinating polyneuropathy (CIDP) and beyond.
2024 has been a blockbuster year for immunology and inflammation (I&I) innovation and investment, driven by the substantial addressable patient populations, enhanced understanding of disease pathophysiology, and the development of novel modalities that can precisely modulate immune activation. These advancements, coupled with the broad indication expansion potential for novel anti-inflammatory therapies, underscore why I&I remains a key strategic priority for B Capital.
NVG-2089: Modulating Immune Function by Mimicking the Action of Sialylated Immunoglobulin G (IgG)
Nuvig’s lead program, NVG-2089, is a novel recombinant Fc fragment that effectively mimics the anti-inflammatory mechanism of IVIg (intravenous immunoglobulin).
Recent research has shown that the anti-inflammatory effect of high-dose intravenous immunoglobulin (IVIg) is largely due to Fc sialylation. Only a small portion (5-15%) of the antibodies in IVIg are sialylated (coated with a sugar group called sialic acid). Despite representing a minority of the antibodies in IVIg, these sialylated antibodies are largely responsible for the strong anti-inflammatory effect of IVIg. They bind to specific receptors on immune cells called type II Fcγ receptors, which then triggers a series of events that reduce inflammation.
Nuvig has developed NVG-2089, a drug designed to mimic the action of the sialylated IgG that drive the efficacy of IVIg. When NVG-2089 is administered, it modulates immune function by:
- Upregulating the inhibitory receptor FcγRIIB on B cells and myeloid cells, which helps to reduce excessive immune activation.
- Promoting the expansion of regulatory T cells (Tregs), which reduce inflammation by suppressing effector T cell function.
- Modulating the levels of various cytokines to decrease the activity of multiple pro-inflammatory pathways throughout the body.
These combined effects support a pleiotropic immunomodulatory mechanism that results in the overall abatement of inflammation. NVG-2089 is poised to address the underlying pathophysiology behind numerous autoimmune diseases while offering a novel non-immunosuppressive treatment option for these patients.
NVG-2089: Revolutionizing Autoimmune Treatment by Addressing IVIg’s Key Limitations
As a novel recombinant product, NVG-2089 may achieve similar efficacy as IVIg at a lower dose while overcoming many of IVIg’s current limitations.
High-dose IVIg has become a mainstay treatment for numerous autoimmune diseases, resulting in a cumulative worldwide market of over $16B today. While IVIg is effective in treating these diseases, it possesses several key limitations:
- IVIg is a donor-derived blood product, leading to supply challenges and variable efficacy and tolerability between batches.
- The extremely high required doses (up to 2g/kg) for IVIg lead to long and burdensome 10-hour infusions that negatively impact patient quality of life.
- IVIg may cause flu-like symptoms and carries a black box warning for thromboembolic events.
As a more potent product that has distilled the therapeutic component of IVIg, NVG-2089 is positioned to overcome each of these limitations while maintaining (or exceeding) the strong efficacy that has established IVIg as a leading treatment option in multiple autoimmune indications. By reducing infusion times and offering a more consistent, scalable recombinant alternative, NVG-2089 has the potential to improve both accessibility and patient outcomes.
Expanding Beyond CIDP: NVG-2089’s Path to Broad Autoimmune Applications
Chronic inflammatory demyelinating polyneuropathy (CIDP) represents a promising lead indication for NVG-2089 proof-of-concept, as high dose IVIg is the standard-of-care for CIDP today. While CIDP alone represents a large market opportunity, with over $4B annual sales for IVIg, significant additional value for NVG-2089 will be unlocked through its broad indication expansion potential to other autoimmune indications. This potential development path parallels the strategy taken by companies developing FcRn antagonists like argenx, whose current market cap exceeds $30B. By pursuing robust clinical validation and addressing key enduring unmet needs, Nuvig aims to position NVG-2089 as a cornerstone therapy for numerous patients with autoimmune diseases.
Partnering with Nuvig’s Team to Advance Immunomodulatory Therapies
Nuvig boasts an exceptional scientific and clinical team, helmed by Pam Conley, PhD, Greg Coffey, PhD, and Alan Glicklich, MD — all of whom bring a proven biotech track record and deep expertise in immunology and drug development. Pam and Greg co-founded Nuvig after their previous company, Portola Pharmaceuticals, was acquired by Alexion Pharmaceuticals for $1.4B in 2020. Alan later joined Nuvig from Chinook Therapeutics, where he served as Chief Medical Officer and helped design and operationalize the studies that led to its $3.2B acquisition by Novartis. These impressive track records and deep therapeutic area expertise are key qualities that we look for in a biotech management team.
We look forward to supporting Nuvig as the company continues to advance its pipeline of immunomodulatory therapies!
LEGAL DISCLAIMER
All information is as of 11.19.2024 and subject to change. The investment discussed herein is a portfolio company of B Capital; however, such investment does not represent all B Capital investments. Certain statements reflected herein reflect the subjective opinions and views of B Capital personnel. Such statements cannot be independently verified and are subject to change. Reference to third-party firms or businesses does not imply affiliation with or endorsement by such firms or businesses. It should not be assumed that any investments or companies identified and discussed herein were or will be profitable. Past performance is not indicative of future results. The information herein does not constitute or form part of an offer to issue or sell, or a solicitation of an offer to subscribe or buy, any securities or other financial instruments, nor does it constitute a financial promotion, investment advice or an inducement or incitement to participate in any product, offering or investment. Much of the relevant information is derived directly from various sources which B Capital believes to be reliable, but without independent verification. This information is provided for reference only and the companies described herein may not be representative of all relevant companies or B Capital investments. You should not rely upon this information to form the definitive basis for any decision, contract, commitment or action.