On March 14, 2024 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported its operational and financial results for the full year ended December 31, 2023 (Press release, Autolus, MAR 14, 2024, View Source [SID1234641179]).
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"We’re delighted to be starting 2024 in such a strong financial position; our recently announced strategic alliance with BioNTech, coupled with two equity financing transactions, raised gross proceeds of $600 million. Combined with our 2023 ending cash of $240 million, this enables us to drive the full launch and commercialization of obe-cel in r/r adult ALL and establish Autolus as a potential leader in the delivery of CAR T therapy to patients with autoimmune diseases," said Dr. Christian Itin, Chief Executive Officer of Autolus.
"2023 was a transformational year for the Company. Our lead program, obe-cel, demonstrated strong data in B-ALL in the pivotal FELIX study, we fully validated our commercial manufacturing facility, The Nucleus, to support our regulatory submissions and we submitted our first BLA for obe-cel to the United States Food and Drug Administration (FDA) in November, with a PDUFA target action date of November 16, 2024. We also just submitted an MAA to the European Medicines Agency (EMA).
"Beyond B-ALL, we see a significant opportunity for obe-cel in autoimmune disease. Our Phase 1 dose confirmation trial in refractory SLE is now open for enrollment. We believe obe-cel’s clinical profile, together with our commercial product delivery base and infrastructure, will help to drive an accelerated and differentiated expansion in autoimmune diseases and we look forward to sharing initial data from the study in late 2024.
"For now, we remain fully focused on preparing for a potential obe-cel launch and successfully transitioning Autolus to a commercial stage company. Pre-commercial and product delivery activities are well underway, and we are on track to make obe-cel available to B-ALL patients as soon as possible, following a potential approval."
Key obecabtagene autoleucel (obe-cel) updates and anticipated milestones:
Obe-cel in relapsed / refractory (r/r) adult ALL – The FELIX Study
Obe-cel BLA for r/r B-ALL submitted to the FDA in November 2023; PDUFA target action date of November 16, 2024. A marketing authorization application (MAA) to the European Medicines Agency (EMA) was just submitted and an MAA submission to the MHRA in the UK is planned for the second half of 2024.
Pooled analysis of the FELIX Phase 1b/2 study presented at ASH (Free ASH Whitepaper) in December 2023 demonstrated prolonged event free survival and low overall immunotoxicity across all cohorts in r/r B-ALL, and particularly in patients with low leukemic burden at lymphodepletion. Additionally, data from a pooled analysis from the ALLCAR19 study and FELIX Phase 1b in r/r B-ALL showed durable remissions with obe-cel as a stand-alone therapy in a subset of patients after a median follow up of >3 years. Further long-term data from the FELIX study is anticipated at medical conferences in 2024.
Obe-cel in B-cell mediated autoimmune diseases
The Phase 1 dose confirmation study in refractory systemic lupus erythematosus (SLE) patients has the first site open for enrollment; initial clinical data expected in late 2024.
Pipeline clinical trials, in collaboration with University College London (UCL), updates and anticipated milestones:
AUTO8 in Multiple Myeloma – Phase 1 MCARTY Study
AUTO8 is a next-generation product candidate for multiple myeloma, which includes two CARs for the multiple myeloma targets, BCMA and CD19. Initial data from the MCARTY Phase 1 study in multiple myeloma presented at ASH (Free ASH Whitepaper) in December 2023 showed AUTO8 was well tolerated, with responses observed in all patients. Further updates from the MCARTY study are anticipated during 2024.
AUTO6NG in Neuroblastoma – Phase 1 MAGNETO Study
AUTO6NG contains a CAR that targets GD2 alongside additional programming modules to enhance the activity and persistence. A Phase 1 clinical study in children with r/r neuroblastoma was opened for enrollment in the fourth quarter of 2023.
Post-period:
Strategic developments:
Strategic alliance with BioNTech SE
In February 2024, BioNTech and Autolus announced a strategic CAR T cell therapy collaboration to advance their pipelines and expand late-stage programs, for $50 million cash upfront and up to $582 million in potential option exercise and milestone payments. Additionally, Autolus sold $200 million of ADSs to BioNTech in a concurrent private placement financing transaction.
Overview:
BioNTech has right to utilize Autolus’ manufacturing capacity, know-how and cost-efficiencies to accelerate the planned clinical development and commercialization of BNT211
BioNTech to support launch and expansion of development program of Autolus’ lead cell therapy candidate obe-cel and will receive a royalty on net sales
BioNTech has co-commercialization options for Autolus’ AUTO1/22 and AUTO6NG programs, and an option to access a suite of Autolus target binders and cell programming technologies
Underwritten offering
In February 2024, Autolus completed an underwritten registered direct offering in the United States at a price of $6.00 per ADS, for total gross proceeds of $350 million.
Recent Operational Updates:
In March 2024, following the most recent GMP inspection by the MHRA in February 2024, The Nucleus manufacturing facility in Stevenage obtained a Manufacturer’s Importation Authorization (MIA), together with the accompanying GMP certificate. This authorization enables Autolus to manufacture products for global commercial and clinical supply at The Nucleus, effective as of March 18, 2024.
In February 2024, Autolus promoted Dr. Chris Williams to Chief Business Officer and Alex Driggs to Senior Vice President, Legal Affairs and General Counsel. Chris has been with the Company since its inception, having negotiated on behalf of UCL the spin off and formation of Autolus. Alex has been with Autolus since 2018 in the role of General Counsel.
Dr. Edgar Braendle has notified the Company that he will step down as Chief Development Officer to pursue other opportunities. Edgar will continue to advise the company during the BLA and MAA review process. Miranda Neville, SVP and obe-cel Program Leader will run the Development team.
Autolus announced the appointment of Elisabeth (Lis) Leiderman, M.D. and Robert W. Azelby to its Board of Directors. Dr. Leiderman brings extensive transactional and financial expertise, and Mr. Azelby brings more than 30 years of biopharmaceutical leadership and commercial experience to Autolus’ Board.
Scientific Publications:
In January 2024, Autolus announced the publication of a paper in ACS Chemical Biology entitled: ‘Designer small molecule control system based on Minocycline induced disruption of protein-protein interaction’ – Jha et al., ACS Chemical Biology (2024) doi:10.1021/acschembio.3c00521; [Link]
In February 2024, Autolus announced the publication of a paper in Nature Communications entitled: ‘Structure-Guided Engineering of Immunotherapies Targeting TRBC1 and TRBC2 in T Cell Malignancies’ – Ferrari et al., Nat Commun 15, 1583 (2024) doi:10.1038/s41467-024-45854-3; [Link]
In March 2024, Autolus announced the publication of a paper in Blood Cancer Journal entitled: ‘Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry – Horna et al., Blood Cancer J. 14, 34 (2024) doi: 10.1038/s41408-024-01002-0; [Link]
2024 Expected News Flow:
Obe-cel FELIX data update at ASCO (Free ASCO Whitepaper), EHA (Free EHA Whitepaper) & ASH (Free ASH Whitepaper) June & Dec 2024
Obe-cel Marketing Authorization Application to MHRA Second half 2024
Obe-cel U.S. FDA PDUFA target action date November 16, 2024
Obe-cel in autoimmune disease – initial data from SLE Phase 1 study Late 2024
Financial Results (Unaudited) for the Full Year Ended December 31, 2023
Cash and cash equivalents at December 31, 2023 totaled $239.6 million, as compared to $382.4 million at December 31, 2023.
Total operating expenses, net for the year ended December 31, 2023, were $179.7 million, as compared to $143.4 million, for the year ended December 31, 2022.
Research and development expenses increased from $117.4 million to $130.5 million for the year ended December 31, 2023, compared to the same period in 2022. This change was primarily due to increases in operating costs related to the Company’s new commercial manufacturing facility, contractual milestone payments and employee salaries and related costs, a decrease in our U.K. reimbursable R&D tax credits claimable through the U.K. small and medium-sized entity (SME) scheme and partially offset by decreases in clinical and manufacturing costs related to the Company’s obe-cel clinical product candidate.
In prior years, Autolus reported the R&D tax credits as income tax benefit on its statements of operations. The Company has revised its financial presentation, including the prior years, and will now present such tax credits as a reduction in research and development expense. As a result, income tax benefit has reduced by $19.5 million and $24.6 million for the years ended December 31, 2023, and 2022, respectively, with corresponding reductions in research and development expenses and total operating expenses.
General and administrative expenses increased from $31.9 million to $46.7 million for the year ended December 31, 2023, compared to the same period in 2022. This increase was primarily due to salaries and other employment-related costs driven by an increase in general and administrative headcount supporting the overall growth of the business, primarily relating to pre-commercialization activities.
Net loss attributable to ordinary shareholders was $208.4 million for the year ended December 31, 2023, compared to $148.8 million for the same period in 2022. The basic and diluted net loss per ordinary share for the year ended December 31, 2023, totaled $(1.20), compared to a basic and diluted net loss per ordinary share of $(1.57) for 2022.
Autolus estimates that, with its current cash and cash equivalents and proceeds received from the strategic alliance with BioNTech and the private placement and underwritten equity financing, it is well capitalized to drive the full launch and commercialization of obe-cel in r/r adult ALL as well as to advance its pipeline development plans, which includes providing runway to data in the first pivotal study of obe-cel in autoimmune disease.