Investigational NDA Submitted to FDA for CD19+ Lymphoma/Leukemia

An investigational new drug application (NDA) for ALA-101 has been submitted to the FDA for the treatment of CD19-positive non-Hodgkin lymphoma and leukemia, according to a press release from Arovella Therapeutics.¹

ALA-101, an allogeneic chimeric antigen receptor invariant natural killer T-cell (CAR-iNKT) therapy platform, is engineered to express CD19-specific CAR as an off-the-shelf product. The therapy may have several advantages over first-generation CAR T approaches, such as a manufacturing process that is scalable and cost-efficient. ALA-101 will also allow for off-the-shelf dosing, which will reduce the time to treatment for patients with improved access.

With the submission of the investigational NDA, a progression toward the first-in-human phase 1 trial can now commence. Typically, within 30 days of submission, the FDA will review the application.

Safety, tolerability, pharmacokinetics, and preliminary antitumor activity of ALA-101 will be studied in the planned phase 1 trial. Receiving the investigational NDA will allow for clinical trials to open in the US instead of Australia alone and will allow the use of the clinical trial notification scheme to conduct phase 1 trials as opposed to the lengthier clinical trial application pathway.

“Filing the [investigational NDA] for ALA-101 is an excellent milestone for Arovella, and we look forward to receiving the feedback from the FDA. It reflects the strength of our scientific and manufacturing foundations and marks the company’s transition toward becoming a clinical-stage biotechnology company,” Michael Baker, PhD, MBA, CEO and managing director of Arovella Therapeutics, said in the press release.¹

Plans to begin the phase 1 trial are set for early 2026.²

In September 2025, at the Australia Securities Exchange Small and Mid-Cap Conference, Baker announced additional plans to expand the ALA platform, including ALA-105. This treatment will target CLDN18.2 for patients with gastric and pancreatic cancer. ALA-105 will incorporate the IL-12 transmembrane technology and will further advance the pipeline.

The company has additional plans to continue manufacturing treatments surrounding hematologic and solid tumor indications.

“Our strategy is to build a portfolio of differentiated cell therapies based on the unique biology of iNKT cells. We believe this platform has the potential to deliver safe, more effective, and more accessible treatments for patients with both blood cancers and solid tumors,” Baker said.²

In an additional interview, Baker noted that the use of ALA-101, an off-the-shelf therapy, will not cause graft-vs-host disease like other CAR T-cell therapies.³ The use of CAR-iNKT has the possibility of using manufactured iNKT donated from one person and administered to another, as they only target the same universal antigen found in every human. Because of this, CAR-iNKT can be stockpiled and ready for use whenever needed, which would allow for a reduction in manufacturing and give patients therapy faster.

“This means when introduced into a new person’s bloodstream, the cells do not recognize anything as foreign and avoid launching an immune attack on the recipient. That is a big advantage and unlocks the potential to use them in what we call an off-the-shelf fashion,” Baker concluded.³

References

1. Arovella files IND with the U.S. FDA for ALA-101 phase 1 clinical trial. News release. Arovella Therapeutics. December 30, 2025. Accessed January 2, 2026. https://tinyurl.com/yc22zuek
2. Arovella showcases iNKT cell therapy platform at ASX SMIDCaps Conference. Biotech Dispatch. September 24, 2025. Accessed January 2, 2026. https://tinyurl.com/4db7cw8c
3. Arovella tackles CAR-T’s limitations in cancer treatment with off-the-shelf innovation. Australian. April 17, 2025. Accessed January 2, 2026. https://tinyurl.com/cdmyxcrt