On August 4, 2022 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 second quarter ended June 30, 2022 (Press release, Autolus, AUG 4, 2022, View Source [SID1234617590]).
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"Autolus has had a successful second quarter, with progress made across all fronts. We were awarded Regenerative Medicine Advanced Therapy (RMAT) Designation for obecabtagene autoleucel (obe-cel) for the treatment of adult acute lymphoblastic leukemia (ALL) by the US Food and Drug Administration (FDA) in April 2022, showcased cell programming technology at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) meeting in May 2022, and announced first clinical data from four pipeline programs at the European Hematology Association (EHA) (Free EHA Whitepaper) congress in June 2022. During this time, we also continued to progress the pivotal Phase 2 FELIX clinical trial of obe-cel in r/r ALL, and the build of our commercial manufacturing site is progressing on schedule," said Dr. Christian Itin, CEO of Autolus. "Obe-cel continues to show very encouraging activity with a high level of sustained complete remissions in B-NHL patients, without inducing severe CRS or neurotoxicity, and AUTO1/22 reached clinical proof of concept with a high level of activity observed in children with ALL who are not eligible for commercial CAR T therapy. We are particularly excited about AUTO4 reaching clinical proof of concept in patients with T cell lymphoma. We are looking forward to releasing initial results for the FELIX trial in Q4 2022 and are planning updates on our other clinical studies at the end of the year."
Key Pipeline Updates:
Obecabtagene autoleucel (obe-cel) in relapsed / refractory (r/r) adult ALL
The FELIX Phase 2 trial continues to progress well, and Autolus is on track to report initial results from the trial in Q4 2022. The Company continues to expect to report full data in H1 2023, with plans to present this data at a medical conference in mid-2023.
Following the RMAT designation granted to obe-cel in April 2022 by FDA, Autolus met with the FDA to review the regulatory pathway for obe-cel in r/r ALL. Consistent with prior guidance, and assuming a positive outcome from the FELIX trial in H1 2023, the Company expects the data to form the basis of a planned Biologics License Application (BLA) submission to FDA.
As previously announced, Autolus initiated a separate cohort of up to 50 additional patients with Minimal Residual Disease (MRD), with the intention of establishing the profile of obe-cel in patients across all levels of disease burden in adult ALL.
Pipeline updates at the European Hematology Congress (EHA) (Free EHA Whitepaper), June 2022:
Obe-cel shows high level of sustained clinical activity in r/r B-NHL patients – ALLCAR19 Extension Trial
Patients continue to be enrolled into the Phase 1 ALLCAR19 extension trial. The latest data readout from this extension study of obe-cel in patients with r/r B-Cell Non-Hodgkin’s Lymphoma (B-NHL) and Chronic Lymphocytic Leukemia (CLL) were presented at EHA (Free EHA Whitepaper) in June 2022. In this patient population, obe-cel continues to display a favorable safety profile with no neurotoxicity/immune effector cell-associated neurotoxicity (ICANS) or Grade ≥ 3 Cytokine Release Syndrome (CRS). Long term persistence of obe-cel in the peripheral blood was demonstrated by qPCR. Of the 20 patients evaluable for efficacy, the overall response rate was 18/20 (90%). In the B-NHL cohorts the CRR was 16/17 (94%) (FL: 7/7, MCL: 3/3, DBCL: 6/7). In the CLL cohort 2/3 patients achieved a PR, notably both achieved MRD-negativity in their marrow and both remain in PR at 10 and 6 months respectively. Of the responding MCL, DLBCL, FL and CLL patients, 17/18 (94%) are without disease progression at last follow-up. One MCL patient relapsed six months following treatment and 1 FL patient died in CR from COVID-19. Longer follow-up and enrolment of additional MCL, FL, DLBCL and CLL patients is ongoing.
Obe-cel shows first activity in Primary CNS Lymphoma – CAROUSEL Trial
Patients continue to be enrolled into the Phase 1 CAROUSEL trial. Data from the trial were presented at EHA (Free EHA Whitepaper) in June 2022, where excellent expansion was observed in the peripheral blood by qPCR, with persistence in all treated patients at last follow-up. No Grade 3 or higher CRS was observed using IV or I-VEN AUTO1 administration. Two cases of Grade 3 ICANS were reported following IV infusion. In the first case the patient had several neurological deficits that evolved despite ICANS treatment and were compatible with progressive PCNSL, as confirmed with the month 1 MRI scan. The second case was a patient whose neurological deficits improved with steroids/anakinra. Encouraging response rates were observed: of 6 patients evaluable for efficacy following IV AUTO1, the ORR was 4/6 (67%), with 2 CRs and 2 PRs. These four responding patients are without disease progression at last follow up. Two patients died from progressive PCNSL on study.
AUTO1/22 in pediatric ALL demonstrates encouraging and durable responses in children ineligible for commercial CAR T product – CARPALL Trial
Autolus, in collaboration with UCL, continues to enroll patients into the AUTO1/22 Phase 1 CARPALL trial. The results from 11 treated patients, who were ineligible for receiving commercial CAR T therapy, were presented in an oral presentation at EHA (Free EHA Whitepaper) in June 2022. AUTO1/22 has demonstrated a favorable safety profile with no incidences of severe CRS, and one Grade 4 ICANS which was indistinguishable from chemotherapy-related leukoencephalopathy. We have seen excellent CAR T expansion, with only 4 patients losing CAR T persistence at the last follow up. Overall, 9 out of 11 patients achieved a molecular complete response, with 2 non-responders. Notably, 2 out of 3 patients with CD19-negative disease achieved molecular complete response demonstrating the efficacy of the CD22 CAR. Two patients relapsed with CD19+CD22+ disease. No antigen negative relapses were seen in responding patients. At a median follow up of 8.7 months, 6 of 9 responding patients were in MRD-negative complete remission (1-12 months) and the median duration of B-cell aplasia has not been reached.
AUTO4 shows high level of clinical activity with a novel targeting approach for patients with T Cell Lymphoma – LibrA T1 Trial
Autolus continues to enroll patients into the AUTO4 Phase 1 clinical trial. Interim Phase 1 data were presented as an oral presentation at EHA (Free EHA Whitepaper) in June 2022 from 10 patients with TRBC1-positive r/r T-cell lymphoma (Peripheral T-cell lymphoma Not Otherwise Specified (PTCL-NOS), Angioimmunoblastic T-cell lymphoma (AITL), Anaplastic Large cell lymphoma (ALCL)) in a Phase 1 dose escalation trial. The median prior lines of treatment was 3 (1-5) and three patients had prior stem cell transplantation. After lymphodepletion with Flu/Cy, patients received either 25, 75, 225 or 450 x 106 CAR T cells. AUTO4 demonstrated a tolerable safety profile, with no patient experiencing any dose limiting toxicities, and no ICANS and no Grade 3 or higher infections. CRS was only seen at the highest dose level of 450 x 106 CAR T cells (Grade 3 in 1 patient; Grade 1-2 in 3 patients). As of April 26, 2022, 9 patients were evaluable for efficacy. At the highest dose level 3 of the 3 patients dosed achieved a complete metabolic remission (CMR) at 1 month. 2 of these patients remain in ongoing CMR by PET-CT at Month 3 and 6 respectively, whilst the 3rd relapsed at 3 months.
Other pipeline updates:
AUTO8 in Multiple Myeloma – MCARTY Trial
Autolus, in collaboration with UCL, initiated a Phase 1 clinical trial of AUTO8, the Company’s next-generation product candidate for multiple myeloma, in Q1 2022, with the first patient dosed during the quarter. AUTO8 comprises two independent CARs targeting BCMA and CD19 designed to induce deep and durable responses and extend the durability of effect.
Autolus presented three abstracts at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) meeting in May 2022. The three abstracts focused on Autolus’ modular approach to CAR T product development, using innovative technology to improve our pipeline of precise, controlled and highly active products. The three abstracts covered: 1) enhancing CAR T therapy using constitutively active cytokine receptors, 2) engineering CAR T cells to express a Fas-CD40 to increase its persistence and tumor cytotoxicity and 3) developing a minocycline mediated protein-protein displacement platform to make cell therapies tunable, dose dependent and reversible.
Key Operational Updates during Q2 2022
The build phase of the Company’s new 70,000 square foot commercial manufacturing facility in Stevenage, UK continues to progress on track with the anticipated schedule. This facility is expected to be ready for Good Manufacturing Practice (GMP) operations by H2 2023 and is designed for a capacity of 2,000 batches per year with the option to expand capacity as needed.
Key Anticipated Clinical Milestones:
Initial clinical results from the pivotal FELIX Phase 2 trial in Q4 2022 and Autolus plans to present full data at a medical meeting in H1 2023.
Longer-term follow up data from Phase 1 ALLCAR19 extension trial of obe-cel in patients with r/r B-NHL and CLL planned in H2 2022.
Longer-term follow up data from Phase 1 CAROUSEL trial of obe-cel in patients with Primary CNS Lymphoma planned in 2023.
Longer-term follow up data from the Phase 1 CARPALL extension trial of AUTO1/22 in pediatric ALL patients planned in H2 2022.
Longer-term follow up data from Phase 1 LibrA T1 trial of AUTO4 in patients with Peripheral T Cell Lymphoma planned in H2 2022.
AUTO6NG Phase 1 clinical trial in patients with neuroblastoma expected to start H2 2022. First data is expected in H2 2023.
AUTO8 Phase 1 MCARTY clinical trial in patients with multiple myeloma has started, with the first patient dosed. First data is expected in H2 2023.
Financial Results for the Quarter Ended June 30, 2022
Cash at June 30, 2022, totaled $216.4 million, as compared to cash of $310.3 million at December 31, 2021.
Total operating expenses for the three months ended June 30, 2022, were $46.5 million, as compared to total operating expenses, net of grant income and license revenue of $1.6 million, of $37.7 million for the same period in 2021.
Research and development expenses increased by $6.1 million to $38.2 million from $32.1 million for the three months ended June 30, 2022 as compared to the same period in 2021. The net increase in research and development expenses of $6.1 million was primarily due to:
an increase of $3.5 million in clinical costs and manufacturing costs primarily relating to the obe-cel clinical product candidate,
an increase of $1.4 million in salaries and other employment related costs including share-based compensation expense, which is mainly driven by an increase in the number of employees engaged in research and development activities,
an increase of $1.4 million in legal fees and professional consulting fees in relation to the Company’s research and development activities,
an increase of $0.5 million related to information technology infrastructure and support for information systems related to the conduct of clinical trials and manufacturing operations,
a decrease of $0.5 million in facilities costs related to the termination and closure of the Company’s US manufacturing facility in 2021 and shift in its manufacturing strategy, and
a decrease of $0.2 million in depreciation and amortization related to property, plant and equipment and intangible assets.
General and administrative expenses increased by $1.1 million to $8.3 million for the three months ended June 30, 2022 from $7.2 million for the three months ended June 30, 2021 primarily due to:
an increase of $1.3 million in salaries and other employment related costs including share-based compensation expenses, which was mainly driven by an increase in the number of employees engaged in general and administrative activities,
an increase of $0.1 million primarily related to higher directors’ and officers’ liability insurance premiums, professional fees and information technology costs,
a decrease of $0.2 million in facilities costs related to the termination by the Company of certain lease agreements in the prior year, and
a decrease of $0.1 million in depreciation and amortization related to property, plant and equipment and intangible assets.
Other expense, net decreased by $0.5 million to $1.3 million for the three months ended June 30, 2022 from $1.8 million for the three months ended June 30, 2021, relating primarily due to the strengthening of the U.S. dollar exchange rate relative to the pound sterling.
Interest expense increased to $1.8 million for the three months ended June 30, 2022 and relates to the liability related to sales of future royalties and sales milestones which arose upon the Company’s entry into the strategic collaboration and financing agreement with Blackstone, in November 2021. There was no interest expense during the comparable period in 2021.
Income tax benefit increased by $1.1 million to $7.5 million for the three months ended June 30, 2022 from $6.4 million for the three months ended June 30, 2021 due to an increase in qualifying research and development expenditures for the quarter.
Net loss attributable to ordinary shareholders was $42.1 million for the three months ended June 30, 2022, as compared to $33.2 million for the same period in 2021. The basic and diluted net loss per ordinary share for the three months ended June 30, 2022, totaled $(0.46) compared to a basic and diluted net loss per ordinary share of $(0.47) for the three months ended June 30, 2021.
Autolus estimates that its current cash on hand and anticipated milestone payments from Blackstone extends the Company’s runway into 2024.
Conference Call
Management will host a conference call and webcast at 8:30 am ET/1:30 pm BST to discuss the Company’s financial results and provide a general business update. Conference call participants should pre-register using this link to receive the dial-in numbers and a personal PIN, which are required to access the conference call. The conference call system has changed, so please make sure you dial in 15 minutes before to ensure timely access to the call.
A simultaneous audio webcast and replay will be accessible on the events section of Autolus’ website.