Autolus Therapeutics plc (NASDAQ:AUTL) is a biopharmaceutical company developing next-generation programmed T cell therapies for the treatment of cancer and autoimmune diseases. The company's lead product candidate, obecabtagene autoleucel (obe-cel), has demonstrated promising results in clinical trials for relapsed/refractory adult B-cell Acute Lymphoblastic Leukemia (r/r B-ALL), and the company has recently submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA). Additionally, Autolus is exploring the potential of obe-cel in autoimmune diseases, with a Phase 1 dose confirmation study in refractory systemic lupus erythematosus (SLE) currently underway.

Business Overview

Autolus was founded in 2014 and is headquartered in London, United Kingdom. The company's core focus is on developing precisely targeted, controlled, and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms, and attack and kill these cells. Autolus believes its programmed T cell therapies have the potential to be best-in-class and offer patients substantial benefits over the existing standard of care, including the potential for cure in some patients.

The company's lead product candidate, obe-cel, is a CD19-targeted CAR-T therapy that has shown promising results in the treatment of r/r B-ALL. In November 2023, Autolus submitted a BLA to the FDA for obe-cel, with a Prescription Drug User Fee Act (PDUFA) target action date of November 16, 2024. The company has also submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) for obe-cel in r/r B-ALL, and plans to submit an application to the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) in the second half of 2024.

In addition to obe-cel, Autolus has a pipeline of other product candidates, including AUTO1/22 and AUTO6NG, which are being developed for the treatment of multiple myeloma and neuroblastoma, respectively. The company is also exploring the potential of obe-cel in autoimmune diseases, with a Phase 1 dose confirmation study in refractory SLE currently underway.

Financials

Autolus reported annual net income of -$208,383,000, annual revenue of $1,698,000, annual operating cash flow of -$145,587,000, and annual free cash flow of -$156,573,000 in its most recent fiscal year. For the first quarter of 2024, the company reported a net loss of $52.7 million, compared to a net loss of $39.8 million in the same period of the prior year. The increase in net loss was primarily due to higher research and development expenses, as well as increased general and administrative expenses related to the company's commercial readiness activities.

As of March 31, 2023, Autolus had cash and cash equivalents of $758.5 million, compared to $239.6 million as of December 31, 2022. The significant increase in cash and cash equivalents was primarily due to the company's strategic alliance with BioNTech SE and a $326.8 million underwritten equity offering completed in February 2023.

Obe-cel: Promising Results in Relapsed/Refractory B-ALL

Autolus' lead product candidate, obe-cel, has demonstrated promising results in the treatment of r/r B-ALL. The company's FELIX study, a Phase 1b/2 clinical trial, has shown prolonged event-free survival and low overall immunotoxicity across all cohorts of patients with r/r B-ALL, particularly in those with low leukemic burden at the time of lymphodepletion.

The FELIX study included patients with a wide range of disease burden, from those with less than 5% tumor burden to those with up to 100% tumor burden. The data showed that patients with low tumor burden (less than 5%) had exceptional outcomes, with a high overall response rate and a very attractive long-term event-free survival. Patients with moderate tumor burden (5% to 75%) also demonstrated a stabilization of the event-free survival curve, indicating the potential for long-term benefit. Even patients with high tumor burden (more than 75%) showed substantially better outcomes compared to historical data for the standard of care, Blincyto.

Importantly, the FELIX study also demonstrated that the safety profile of obe-cel was favorable, with low rates of high-grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Patients with low tumor burden at the time of lymphodepletion experienced no high-grade CRS or ICANS events, while those with moderate tumor burden had relatively low rates of these adverse events.

Obe-cel in Autoimmune Diseases: Exploring New Frontiers

In addition to its promising results in r/r B-ALL, Autolus is also exploring the potential of obe-cel in the treatment of autoimmune diseases. The company has initiated a Phase 1 dose confirmation study of obe-cel in refractory SLE, with the first two patients enrolled during the first quarter of 2023. The company expects to report initial data from this study by the end of 2024.

The rationale for using obe-cel in autoimmune diseases is based on the observation that the product's unique design, with a faster off-rate of the CD19 binder, may result in a shorter persistence of the CAR-T cells in these patients compared to the persistence seen in the treatment of pediatric ALL. This shorter persistence may be better suited to the autoimmune setting, where the goal is to reset the immune system without the risk of long-term persistence and potential complications.

Autolus is closely monitoring the emerging data from other research groups exploring the use of CAR-T therapies in autoimmune diseases, such as the work done at the University of Erlangen. While the initial results have been promising, the company cautions that the data is still limited, and there is much to be learned about the optimal use of these therapies in autoimmune settings.

Strategic Collaboration with BioNTech

In February 2023, Autolus announced a strategic collaboration and financing agreement with BioNTech SE. Under the terms of the agreement, BioNTech made an upfront payment of $40 million to Autolus in exchange for the rights to future revenues from the sales of obe-cel products. BioNTech also has the option to co-fund the development of two of Autolus' pipeline programs, AUTO1/22 and AUTO6NG, in return for agreed-upon economic terms, including option exercise fees, milestone payments, and profit-sharing arrangements.

Additionally, the agreement grants BioNTech the option to negotiate a joint manufacturing and commercial services agreement with Autolus, which would allow the companies to leverage each other's manufacturing and commercial capabilities, including access to Autolus' commercial site network and infrastructure.

The strategic collaboration with BioNTech provides Autolus with additional financial resources to support the launch and commercialization of obe-cel, as well as the advancement of its pipeline programs. The agreement also strengthens the company's relationship with a leading player in the field of cell and gene therapies, potentially opening up new opportunities for collaboration and synergies in the future.

Operational and Corporate Developments

In addition to the progress made with obe-cel and the strategic collaboration with BioNTech, Autolus has also made several important operational and corporate developments during the past year.

The company's new commercial manufacturing facility, known as "The Nucleus," located in Stevenage, United Kingdom, obtained a Manufacturer's Importation Authorization (MIA) and Good Manufacturing Practice (GMP) certificate in March 2023. This authorization enables Autolus to manufacture products for global commercial and clinical supply at The Nucleus, which is a crucial step in preparing for the potential launch of obe-cel.

Furthermore, Autolus has strengthened its board of directors with the additions of Lis Leiderman, Bob Azelby, and Mike Bonney, all of whom bring extensive experience in capital markets, operations, and commercialization. The company has also welcomed Ravi Rao, an expert in immunology and autoimmune diseases, to the board, further bolstering its expertise in the company's expanding focus on autoimmune indications.

Risks and Challenges

Despite the promising progress made by Autolus, the company faces several risks and challenges that investors should be aware of. The successful development and commercialization of obe-cel and the company's other product candidates are subject to significant regulatory, clinical, and commercial uncertainties. Delays or setbacks in the regulatory approval process, manufacturing issues, or difficulties in securing reimbursement for the company's therapies could all have a material impact on Autolus' financial performance and future prospects.

Additionally, the competitive landscape in both the oncology and autoimmune disease spaces is rapidly evolving, with other companies developing their own CAR-T and T cell-based therapies. Autolus will need to continue to innovate and differentiate its products to maintain a competitive edge.

Outlook

Autolus is well-positioned for a transformative year in 2024 and beyond. The company's lead product candidate, obe-cel, has demonstrated promising results in the treatment of r/r B-ALL, and the submission of the BLA to the FDA and the MAA to the EMA mark significant milestones in the product's development. The company's strategic collaboration with BioNTech provides additional financial resources and potential synergies to support the launch and commercialization of obe-cel, as well as the advancement of its pipeline.

Furthermore, Autolus' exploration of obe-cel in autoimmune diseases, such as the ongoing Phase 1 study in refractory SLE, represents an exciting new frontier for the company's technology. While the data in this area is still limited, the potential to leverage Autolus' unique CAR-T design to reset the immune system in autoimmune conditions is intriguing and worth watching closely.

Conclusion

Overall, Autolus appears to be well-positioned for continued growth and value creation. The successful approval and commercialization of obe-cel, coupled with the company's expanding pipeline and strategic collaborations, could position Autolus as a leader in the field of programmed T cell therapies for both oncology and autoimmune indications.