Enhancing Care with NK Cell Therapy: Fred Aslan from Artiva Biotherapeutics in Conversation with PharmaShots

Shots:

Immune reset in oncology has been observed with approved autologous CAR-T products. A recent study published in Nature demonstrated B-cell reconstitution and immune reset in systemic lupus erythematosus (SLE) patients treated with a CD19 autologous CAR-T, showcasing promising potential in autoimmune diseases

Today, at PharmaShots, we have Fred Aslan shedding light on Artiva's AlloNK, an allogeneic, off-the-shelf, cryopreserved NK cell therapy candidate. AlloNK is designed to enhance the antibody-dependent cellular cytotoxicity (ADCC) effect of monoclonal antibodies (mAbs) to drive B-cell depletion

Fred discusses the recently raised funding through Artiva’s IPO, ongoing clinical trials, and the therapeutic strategy utilizing NK cells to advance oncology and autoimmune therapies.

Saurabh: Could you explain the concept of immune reset and its significance in treating autoimmune diseases?

Fred: We believe an immune reset constitutes a deep enough B-cell depletion in the affected tissues, with the B cells reconstituting with a naïve phenotype resulting in a marked clinical response that is durable and where patients are able to be in a drug-free disease remission. In 2022, a study published in Nature led by Dr. George Schett showed that five systemic lupus erythematosus (SLE) patients treated with a CD19 auto-CAR-T achieved a deep enough depletion of B cells resulting in B-cell reconstitution in these patients. In subsequent follow up, these patients remained disease-free with no background medications for multiple years.

This had been seen in oncology with approved auto-CAR-T products but had not been seen before in autoimmune disease. It validated the approach of using a potent B-cell depleting agent in the context of autoimmune disease to produce an “immune reset”.

Saurabh: How does Artiva Biotherapeutics plan to validate the effectiveness of NK cells in achieving drug-free disease remission?

Fred: Artiva’s lead program AlloNK is an allogeneic, off-the-shelf, cryopreserved NK cell therapy candidate designed to enhance the antibody-dependent cellular cytotoxicity (ADCC) effect of monoclonal antibodies (mAbs) to drive B-cell depletion and to be administered in the community setting. Using Artiva’s proprietary cell therapy manufacturing platform, we can generate thousands of doses of cryopreserved, infusion-ready AlloNK from a single cord blood unit.

Our conviction in the transferability of our proposed mechanism of action from treatment of B-cell non-Hodgkin lymphoma (B-NHL) to treatment of autoimmune diseases is driven by both the peer-reviewed scientific publication led by Dr. Schett as well as preliminary data from our ongoing Phase 1/2 clinical trial of AlloNK in combination with rituximab in patients with relapsed or refractory B-NHL. We saw both complete peripheral B-cell depletion in all of our patients treated with the full treatment regimen in our Phase 1/2 B-NHL trial for a prolonged period of time as well as durable complete responses in B-NHL patients as measured by tissue imaging.

Because of the common tissues of interest, principally the lymphoid tissues, in B-NHL and autoimmune diseases, we believe our data in B-NHL provides supporting evidence for our proposed mechanism of action in autoimmune disease. In particular, we believe these data support that AlloNK in combination with B-cell targeted mAbs has the potential to provide deep B-cell depletion and offer therapeutic potential, a differentiated safety profile, and patient accessibility to improve the treatment paradigm for numerous autoimmune diseases.

We are currently exploring AlloNK in two clinical trials, a company-sponsored Phase 1/1b trial in SLE, including patients with lupus nephritis (LN) as well as an investigator-initiated basket trial (IIT) across rheumatoid arthritis (RA), pemphigus vulgaris, vasculitis, and SLE, being conducted in a community rheumatology practice.

Saurabh: What are the key milestones you anticipate in the next 12-18 months regarding your clinical trials?

Fred: We have guided to initial data in the first half of 2025 from at least one of our clinical trials – either the company-sponsored Phase 1/1b trial or the basket IIT.

Saurabh: Why is it important for the treatments to be administered in an outpatient clinic setting rather than in a hospital?

Fred: Today, most patients with autoimmune diseases are seen by community practices, versus in the hospital, and are a younger more active demographic that may not suffer from the same sense of urgency in seeking treatment. Further, requirements of hospitalizations limit the scalability of a therapy. What is lacking today is a therapy that is 1) potent enough that has a potential to achieve a drug free disease remission, 2) safe enough to be administered in an outpatient setting where most of these patients are treated, and 3) scalable enough to be brought to that setting. We believe our lead program AlloNK provides a balance across these three factors.

Saurabh: Can you provide details about the ongoing trials, including the basket trial you mentioned?

Fred: The ongoing company-sponsored Phase 1/1b trial is open-label, exploring AlloNK in combination with CD20-targeting mAbs (rituximab or obinutuzumab) in patients with SLE, with or without LN, who previously failed treatment.

In April 2024, the FDA cleared an IND submitted by Integral Rheumatology & Immunology Specialists (IRIS), a large community practice rheumatology clinic in Florida, to conduct a basket IIT to assess the safety, tolerability, and clinical activity of AlloNK in combination with rituximab in patients with RA, PV, SLE, and the ANCA-associated vasculitis subtypes GPA / MPA. Along with the potential to generate signals across a number of indications, this trial will allow us to demonstrate the ability to utilize our cell therapy approach in a community setting.

Saurabh: How does the recent successful IPO of $179M position Artiva Biotherapeutics for future growth and research initiatives?

Fred: We are excited about having raised the capital through the IPO as we continue to execute on our programs. Our pro forma cash runway is at least through the end of 2026, which gets us through key clinical milestones.

Saurabh: Can you discuss the role of NK cells in your therapeutic strategy and their advantages compared to traditional treatments?

Fred: NK cells are the first line of immune surveillance and defense and naturally work in concert with antibodies. The antibody first binds to a target on a diseased cell, then to the NK cell via CD16 which engages the antibody to mount an ADCC response. NK cells may have an advantage over other immune cells, such as the T-cells used in CAR-T cell therapy and other autologous cell therapies, because they can be used as allogeneic therapies, meaning that NK cells from one donor can be administered to one or many patients without the requirement for gene editing or other genetic manipulations.

As noted above, AlloNK is an allogeneic cell therapy designed to enhance the ADCC effect of mAbs to drive B-cell depletion. We believe AlloNK, versus other modalities or traditional treatments, strikes a nice balance across efficacy, safety, and the scalability and accessibility required to treat patients with autoimmune diseases.

Approved treatments for autoimmune diseases encompass various classes of therapies, including steroids and immunosuppressant drugs. Even though they manage symptoms of disease, many patients still suffer from disease progression, leading to worsening complications. Furthermore, chronic use of these therapies typically creates secondary complications for patients such as risk of infections, cancer, and cardiovascular disease.

We have learned from our experience in oncology that AlloNK plus rituximab has been able to potently deplete B-cells and shown durable responses in aggressive B-NHL patients while maintaining a safety profile that is suitable for community administration. Our current scale at capacity can treat more than 1,000 autoimmunity patients annually at estimated COGS that is less than $6,000.

Further, because AlloNK can be used with mAbs that target different antigens based on the target cell’s antigen expression, we believe we have the versatility to use AlloNK in combination with different mAbs to deplete distinct B-cell subpopulations. We believe this versatility will enable us to pursue a wider range of indications than cell therapies engineered against specific targets.

Image Source: Canva

About the Author:

Fred Aslan

Dr. Aslan has a 20-year track record as an executive and investor in the life sciences industry. Prior to Artiva, he was President and CBO at Vividion Therapeutics. Prior to Vividion, Dr. Aslan had a 12-year affiliation with Venrock. As an investor from 2006 to 2013, he co-founded and served as a board member of Receptos Pharmaceuticals and was involved in the formation of Fate Therapeutics. Subsequently, as an entrepreneur, he founded Adavium Medical and served as CEO until 2018. Earlier in his career he was Director of Corporate Development and Head of Investor Relations at CuraGen and a consultant with the Boston Consulting Group.