On March 4, 2021 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 fourth quarter and full year ended December 31, 2020 (Press release, Autolus, MAR 4, 2021, View Source [SID1234576107]).
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"Autolus’ primary focus is on delivering the potential pivotal AUTO1 program and the company starts 2021 in a position of financial strength, having raised a total of $131 million in gross proceeds this quarter, giving us a cash runway into the first half of 2023," said Dr. Christian Itin, chairman and chief executive officer of Autolus. "We are excited about the unique characteristics of AUTO1 and the significant commercial opportunity that adult Acute Lymphoblastic Leukemia represents. Furthermore, we are committed to building additional value by capitalizing on the unique clinical profile of AUTO1 in additional B Cell malignancies and by progressing our pipeline of CAR T cell therapies, including AUTO1/22 in pediatric ALL, AUTO4 in peripheral T cell Lymphoma and AUTO6NG in solid tumors. As such, we expect multiple clinical proof of concept read outs during 2021 and 2022."
Key Pipeline Updates:
AUTO1 in relapsed / refractory (r/r) adult B-Acute Lymphocytic Leukemia (ALL). Positive data from the ALLCAR Phase 1 clinical trial was presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2020, demonstrating that, as of the November 12, 2020 data cut-off date, AUTO1 was well tolerated, with no patients experiencing ≥ Grade 3 cytokine release syndrome (CRS). Three patients (15%), all of whom had high leukemia burden (>50% blasts), experienced Grade 3 neurotoxicity (NT) that resolved swiftly with steroids. Of the 19 patients evaluable for efficacy, 16 (84%) patients achieved minimum residual disease (MRD)-negative complete response (CR) at one month. Most notably, the durability of remissions is highly encouraging. Across all treated patients, event free survival (EFS) at six and 12 months is 69% and 52% respectively. Median EFS and overall survival (OS) had not been reached at a median follow up of 16.9 months (range up to 30.5 months). Data from the potential pivotal program, FELIX, is expected in 2022.
AUTO1 in indolent B cell Non-Hodgkin Lymphoma (NHL) (cohort 1), high grade B-NHL (cohort 2) and chronic lymphocytic leukemia (CLL) (cohort 3). Autolus reported positive AUTO1 data at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2020. As of the data cut-off date of November 12, 2020, four patients in Cohort 1 had been infused with AUTO1. AUTO1 was well tolerated, with no patients experiencing ≥ Grade 2 CRS and no patients experiencing NT of any grade. All four patients achieved a Complete Metabolic Response (CMR). Autolus is planning to present updated data on AUTO1 in indolent B-cell lymphoma indications at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in June 2021.
AUTO1/22 in pediatric ALL. The first patient was dosed in the extension cohort of the CARPALL clinical trial in Q4 2020. Autolus plans to provide a data update in Q4 2021.
AUTO3 in relapsed/refractory diffuse large B cell lymphoma (DLBCL). Positive data from the Phase 1 ALEXANDER clinical trial was presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2020 demonstrating, as of the October 30, 2020 data cut-off date, AUTO3 was well tolerated, with low rates of CRS and NT. Across all 49 patients, there was only one case of Grade 3 CRS with primary infusion, and only three cases of NT were reported, with two being ≥ Grade 3. As of the data cut-off date, none of the patients achieving a complete response (CR) experienced any NT and all cases of NT observed were seen in a setting of disease progression and with confounding factors. Autolus plans to seek a partner for this program.
AUTO4 in Peripheral T Cell Lymphoma (PTCL). AUTO4 will continue, in 2021, to be evaluated in a dose escalation phase of a Phase 1/2 clinical trial in 2021. Autolus expects to provide a next data update in H2 2021.
AUTO5 in Peripheral T Cell Lymphoma. Positive preclinical data were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) II (AACR) (Free AACR Whitepaper) Annual Meeting in June 2020. The data highlight the specificity and selectivity of the Autolus T cell lymphoma product candidate, AUTO5. Autolus expects to initiate a Phase 1 clinical trial in H2 2021.
AUTO6NG in small cell lung cancer (SCLC). Positive preclinical data were presented at the AACR (Free AACR Whitepaper) Annual Meeting in June 2020. Autolus has designed enhancing modules to specifically overcome tumor microenvironment (TME) defenses in solid tumor settings. The new data reported at the AACR (Free AACR Whitepaper) meeting suggest that AUTO6NG can overcome the immune suppressive mechanisms in the TME. Autolus plans to progress AUTO6NG for evaluation in GD2 positive tumors into the clinic in H2 2021.
AUTO7 in prostate cancer. Positive preclinical data were presented at an oral presentation at the AACR (Free AACR Whitepaper) Annual Meeting in June 2020. AUTO7 uses an optimized CAR to target cancer cells expressing PSMA, even at low levels, and includes modules introduced in AUTO6NG, with a module that activates immune responses at the tumor site through limited secretion of IL-12. The data presented at the AACR (Free AACR Whitepaper) meeting demonstrated that AUTO7 is highly potent in cytotoxicity assays against cells expressing PSMA, even at low levels, and demonstrate the feasibility of this multi-modular cell programming approach in overcoming the immunotherapeutic challenges presented by advanced prostate cancer, which is typically otherwise an immunologically cold tumor. Autolus plans to progress AUTO7 into the clinic in H1 2022.
AUTO8 in multiple myeloma. This program will be explored in a first clinical trial starting mid-2021.
Partnerable Coronavirus Disease (COVID-19) Project. Autolus’ research team has developed a potentially universal SARS-CoV2 decoy receptor with virus neutralizing activity against SARS-CoV2 and its variants and also active against SARS-CoV1.
Operational Highlights:
Autolus sold 1,718,506 ADSs under its at-the-market program with Jefferies, for net proceeds of approximately $15.3 million, in January 2021.
Successful closing of a public offering raising net proceeds to Autolus, after underwriting discounts and commissions, of $108.1 million in February 2021, taking total net cash raised in Q1 2021 to approximately $123.4 million.
As announced in Autolus’ business update in January 2021, the company will be prioritizing the AUTO1 program and plans to partner the AUTO3 program before progressing it into the next phase of development.
Also announced in Autolus’ business update in January 2021, the company will adjust its workforce and infrastructure footprint, which will involve an overall reduction in headcount of approximately 20%. The restructuring remains ongoing and Autolus expects to realize cash savings, on an annualized basis, of approximately $15 million per annum once the operational changes are fully implemented.
As previously announced, Dr. Nushmia Khokhar, Senior Vice President, Clinical Development will be leaving the company in mid-March 2021 and Dr. Adam Hacker, Senior Vice President for Regulatory Affairs and Quality, left the Company in January 2021. The company would like to thank Drs. Khokhar and Hacker for their contributions and wishes them well in the future. A search for a Chief Medical Officer is ongoing.
Appointment of Dr Jay T Backstrom to Autolus’ Board of Directors, effective August 1, 2020. Dr Backstrom currently serves as EVP, Head of Research & Development at Acceleron Pharma Inc. and prior to that served as CMO and Head of Regulatory Affairs at Celgene Corporation.
Key Upcoming Clinical Milestones:
AUTO1 updates in 2021 on ALLCAR19 in patients with r/r B-NHL and longer term follow up of the fully enrolled r/r aALL cohort.
AUTO1 – Currently enrolling Phase 1b/2 pivotal study (FELIX) in r/r adult ALL patients with data expected in 2022.
Updates on Phase 1 programs AUTO1/22 in pediatric ALL, as well as AUTO4 in TRBC1+ Peripheral TCL, in 2021.
Phase 1 trials are expected to be initiated in 2021 with AUTO1 in Primary CNS Lymphoma, AUTO5 in TRBC2+ Peripheral TCL, AUTO6NG in Neuroblastoma, and AUTO8 in Multiple Myeloma.
First exploratory allogeneic program expected to enter the clinic in H1 2021.
Financial Results for the Quarter and Year Ended December 31, 2020
Cash at December 31, 2020 totaled $153.3 million, as compared to $210.6 million at December 31, 2019. In January 2021, the company sold 1.7 million ADSs under its Open Market Sales AgreementSM with Jefferies LLC as sales agent, resulting in net proceeds of $15.3 million and in February 2021, the company conducted a public offering of 16,428,572 ADSs representing 16,428,572 ordinary shares, including the exercise in full by the underwriters of their option to purchase an additional 2,142,857 ADSs, at a public offering price of $7.00 per ADS and net proceeds of $108.1 million.
Net total operating expenses for the twelve months ended December 31, 2020 were $168.1 million, net of grant income and license revenue of $1.7 million, as compared to net operating expenses of $146.1 million, net of grant income of $2.9 million, for the same period in 2019.
Research and development expenses increased to $134.9 million for the year ended December 31, 2020 from $105.4 million for the year ended December 31, 2019. Cash costs, which exclude depreciation and amortization as well as share-based compensation, increased to $116.9 million from $83.4 million. The increase in research and development cash costs of $33.5 million consisted primarily of (i) an increase of $8.8 million in compensation and employment related costs, net of lower travel costs, due to an increase in employee headcount to support the advancement of our product candidates in clinical development and lessened travel due to the COVID-19 pandemic, (ii) an increase of $14.4 million in project expenses as a consequence of the advancement of our clinical portfolio which includes research and process development and manufacturing activities necessary to prepare, activate, and monitor clinical trial programs, (iii) an increase of $6.0 million in facilities costs related to the commencement of a lease for an additional manufacturing suite and the continued scaling of manufacturing operations, (iv) an increase of $4.0 million in IT infrastructure and support for information systems related to the conduct of clinical trials and manufacturing operations, (v) an increase of $0.5 million related to legal fees and (vi) an increase of $1.7 million related to cell logistics, which is offset by a reduction in materials purchases of $0.7 million and license fees of $1.1 million.
Non-cash Research & Development costs decreased to $18.1 million for the year ended December 31, 2020 from $22.0 million for the year ended December 31, 2019. The $3.9 million decrease is related to a decrease of $4.8 million share-based compensation expense as a result of a lower fair value of stock options recognized in the period, offset by a $0.9 million increase in depreciation.
General and administrative expenses decreased to $35.0 million for the year ended December 31, 2020 from $39.5 million for the year ended December 31, 2019. Cash costs, which exclude depreciation as well as share-based compensation increased to $27.4 million from $26.6 million. There were increases of $1.3 million related to D&O insurance costs and intellectual property and $0.1 million of facilities cost, offset by decreases of $0.5 million of compensation and other employment related costs and $0.1 million in general office expense.
Non-cash General and Administrative costs decreased to $7.6 million for the year ended December 31, 2020 from $12.9 million for the year ended December 31, 2019. The decrease of $5.3 million is mainly attributed to lower share-based compensation expenses as a result of the lower fair value of share options recognized during the period.
Interest income decreased to $0.5 million for the year ended December 31, 2020 from $2.5 million for the year ended December 31, 2019. This decrease is due to the lower cash balances held during the year combined with lower interest rates for cash held on deposit. Other income decreased to $1.4 million for the year ended December 31, 2020 from $4.5 million for the year ended December 31, 2019 primarily due to a weakening of the U.S. dollar exchange rate relative to the pound sterling. The decrease of $4.6 million in the year ended December 31, 2020 was offset by lease termination gains of $1.5 million.
The Income tax benefit increased to $24.2 million for the year ended December 31, 2020 from $15.2 million for the year ended December 31, 2019 due to additional U.K. research and development tax credits receivable from HMRC. Research and development credits are obtained at a maximum rate of 33.35% of our qualifying research and development expenses, and the increase in the net credit was primarily attributable to an increase in the company’s eligible research and development expenses.
Net loss attributable to ordinary shareholders was $142.1 million for the twelve months ended December 31, 2020, compared to $123.8 million for the same period in 2019. The basic and diluted net loss per ordinary share for the twelve months ended December 31, 2020 totaled $(2.76) compared to a basic and diluted net loss per ordinary share of $(2.88) for the twelve months ended December 31, 2019.
Autolus estimates that its current cash on hand, which includes the recent financings in January and February 2021, will extend the Company’s runway into H1 2023.
Management will host a conference call and webcast at 8:30 am ET/1:30 pm GMT to discuss the company’s financial results and provide a general business update. To listen to the webcast and view the accompanying slide presentation, please go to the events section of Autolus’ website
The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 2268057. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 2268057.