Artiva Biotherapeutics Goes Public with $167M IPO to Advance Allogeneic NK Cell Therapies for Autoimmune Diseases and Cancer

Jul 26, 2024 07:31 CST Updated 07:31

Artiva Biotherapeutics

Cancer Treatment Drug Developer

Source: PharmaDJ

Text: Ruirui Li Edited by Ohu

NK Cells: Part of the Innate Immune SystemNK cells regulate their activity through the activation and inhibition of receptors on their surface that interact with the environment, including target cells. This balance enables NK cells to recognize and kill abnormal cells while suppressing cytotoxic responses to normal tissues, thereby providing a set of immune effector cells to defend against cancer and virus-infected cells.

Over the past decade, cell therapy has shown great promise in hematologic malignancies and has been the subject of numerous studies in various B-cell-driven autoimmune diseases.

Recently, Artiva Biotherapeutics (Nasdaq: ARTV), a biotechnology company, announced the pricing of its initial public offering. Artiva is committed to developing effective, safe, and accessible cell therapies for patients suffering from devastating autoimmune diseases and cancer. All shares of common stock are issued by Artiva. Prior to deducting underwriting discounts, commissions, and estimated offering expenses payable by Artiva,Artiva Biotherapeutics, Inc. is expected to raise approximately $167 million in gross proceeds from this offering.

PART.01

Advances in the Development of Therapies for Autoimmune Diseases

One of the key roles of the immune system is to attack pathogens, but knowing when to stop the attack is equally crucial. If immune cells perceive the body's own tissues as a threat, they will attack normal cells and cause harm. Autoimmune diseases are characterized by loss of immune tolerance, high chronicity, high morbidity, and high mortality.

For more than 50 years, researchers have been attempting to tame autoimmune diseases (such as Type 1 diabetes, lupus, and multiple sclerosis). Most approved therapies suppress the entire immune response, and conventional immunosuppression or targeted disease-modifying therapies (DMT) often require repeated administration. While this can alleviate symptoms to a certain extent, it increases the risk of infections and even cancer.

Immunologists have long hoped to find ways to restore the immune system's ability to ignore antigens within the body while appropriately attacking those that do not belong. Some researchers have also attempted to selectively eliminate problematic cells or introduce inhibitory immune cells designed to target these cells.

In recent years, novel cell therapies, including mesenchymal stromal cells (MSC), chimeric antigen receptor T cells (CAR-T), and regulatory T cells (Treg), have been successfully applied in the treatment of autoimmune diseases.

NK Cells: A Rising Star in Cell TherapyNK cells can naturally collaborate with antibodies. The antibody first binds to a target on the diseased cell, then connects with NK cells via the CD16 receptor on the cell surface; CD16 binds with the antibody to trigger an ADCC (antibody-dependent cell-mediated cytotoxicity) response.

Compared with T cells used in CAR-T cell therapy and other cell therapies, NK cells tend to have more advantages because they can be used as allogeneic therapies. That is, NK cells from the same donor can be administered to one or multiple patients without requiring genetic editing or other genetic manipulations.

However,One of the biggest technical challenges in the NK cell therapy field is the large-scale, scalable "industrialized" manufacturing process.Large-scale scalability means the ability to produce enough products to treat tens of thousands of patients each year, in other words, requiring millions or even trillions of NK cells. Industrialization means that the product has good characteristics, with consistency between batches and donors, allowing for efficient production.

PART.02

Features and Prospects of Artiva's Pipeline

AlloNK® (also known as AB-101) is a cutting-edge research and development project by Artiva Biotherapeutics.An allogeneic, ready-to-use, non-GMO, cryopreserved NK cell therapeutic candidate, which can enhance the antibody-dependent cellular cytotoxicity of monoclonal antibodies, thereby driving B-cell depletion. AlloNK is currently undergoing clinical trials for systemic lupus erythematosus, applicable to patients with or without lupus nephritis.

AlloNK is also conducting an investigator-initiated basket trial for multiple autoimmune indications. In addition, researchers are evaluating its use in treating non-Hodgkin lymphoma, as well as its combination with Affimed's innate cell engager Acimtamig for the treatment of patients with relapsed/refractory CD30-positive lymphoma.

Figure 1. Schematic diagram of AlloNK therapy (Source:Data Compilation from Public Sources）

Research on autologous CAR T-cell therapies targeting B cells has shown that deep depletion of B cells in autoimmune diseases such as lupus leads to an "immune reset" and complete, durable responses. Therapies combining NK cells with antibodies can overcome many of the limitations associated with autologous CAR-T therapies.Inherent shortcomings:

1. Autologous CAR-T requires customized processing and genetic engineering, and cannot be "off-the-shelf".

2. Compared with CAR-T therapy, NK cell therapy has a lower incidence and severity of adverse reactions, such as lower cytokine release syndrome and neurotoxicity.

3. As a non-GMO cell therapy candidate, AlloNK has not shown the potential risk of secondary malignancies, whereas this risk has been observed in CAR-based cell therapies.

As early as February 22 this year, the U.S. FDA granted AlloNK Fast Track Designation (FTD) for use in combination with rituximab or obinutuzumab to treat lupus nephritis. Artiva Biotherapeutics had previously received FDA approval for a new drug clinical trial application (IND) for AlloNK in combination with rituximab to treat lupus nephritis.Marks the first IND approval for allogeneic off-the-shelf NK cell therapy in autoimmune diseases.

Artiva's product pipeline also includes CAR-NK candidates targeting solid tumors and hematologic cancers. As an alternative to targeting NK cells by combining with monoclonal antibodies or NK engagers, chimeric antigen receptors (CARs) targeting specific antigens can be added to directly target NK cells. This requires genetic modification of NK cells, and cytokine transgenes can also be incorporated to further enhance the activity and persistence of these CAR-NK cells.

Figure 2. Artiva Biotherapeutics' Cell Therapy Pipeline (Source:Data Compilation from Public Sources）

Artiva has built a comprehensive and robust industrial production platform, which has already supported over 35 clinical-scale batches of cell production. This platform, based on pre-selected cord blood, proprietary engineered feeder cells, and carefully selected culture media, achieves robust cell expansion without exhaustion. Among these production batches, the cells demonstrate high consistency between batches and donors, which is essential for any allogeneic off-the-shelf product.

Figure 3. Artiva's Production Platform (Source: Public Data Compilation)

Editor's Note:

In the field of autoimmune disease therapy research and development, the theoretical foundation and clinical experience of innovative cell therapies continue to evolve, bringing together fruitful multidisciplinary collaborations. At the same time, scientific research plays a crucial role in elucidating the mechanisms behind the clinical improvement and control of dysfunctional immune systems in diseases, while also considering short-term toxicity and long-term risks. Innovative companies like Artiva Biotherapeutics, with solid R&D accumulation and robust production capabilities, will continue to attract capital investment.

Reference Source:

1. NK Cell Therapies: How Artiva Biotherapeutics Leverages Its "Manufacturing First" Approach. April 24, 2024

2. https://www.artivabio.com/

3. Greco, Raffaella, et al. "Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee." EClinicalMedicine 69 (2024).

*Disclaimer: This article merely introduces research progress in the pharmaceutical and disease fields, provides a brief overview of research, or shares pharmaceutical-related information. It neither recommends any treatment or diagnostic plans nor constitutes any advice on related investments.If there are any omissions in the content, please feel free to communicate and point them out!

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