Syncona Limited

Autolus presents FELIX data at ASCO

2 June 2023

Syncona Ltd, a leading healthcare company focused on creating, building and scaling global leaders in life science, notes that its portfolio company, Autolus Therapeutics Plc (Nasdaq: AUTL) ("Autolus"), has announced additional data from the pivotal Phase II FELIX study of obe-cel in adult r/r B-cell Acute Lymphoblastic Leukemia (B-ALL) at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. A copy of the announcement is set out below, with key highlights as follows:

·      Obe-cel has demonstrated a response (CR/CRi)[1] of 76% amongst patients dosed in the FELIX study; primary endpoint has already been met based on previously communicated interim analysis

·      Encouraging safety profile with potential best-in-class tolerability; only 3% of patients experienced Grade 3 or higher cytokine release syndrome (CRS), and 7% of patients experienced Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS)[2]

·      Robust and reliable manufacturing and logistics, with 84% of the 112 patients enrolled in the FELIX trial being dosed with obe-cel

Management will host a conference call and webcast today at 4.00pm ET/9.00pm BST to summarize the ASCO data. To listen to the webcast please go to the events section of Autolus' website. Conference call participants should pre-register using this link to receive the dial-in numbers and a personal PIN.

Martin Murphy, Chair of Syncona Investment Management Limited, said: "Today's announcement further highlights the potential of obe-cel to deliver meaningful impact for patients suffering from adult B-ALL. It is encouraging to see response rates rise as increasing numbers of patients have become evaluable for efficacy, with this set of data also further underlining the potentially differentiated safety profile of the drug compared to other alternative CAR-T therapies. We look forward to further updates from the FELIX study throughout the year, which will provide further insight on its potential durability, and to Autolus' planned filing of its BLA with the FDA later in the year as it prepares for the commercial launch of obe-cel."

[ENDS]

Copies of this press release and other corporate information can be found on the company website at: www.synconaltd.com

Forward-looking statements - this announcement contains certain forward-looking statements with respect to the portfolio of investments of Syncona Limited. These statements and forecasts involve risk and uncertainty because they relate to events and depend upon circumstances that may or may not occur in the future. There are a number of factors that could cause actual results or developments to differ materially from those expressed or implied by these forward-looking statements. In particular, many companies in the Syncona Limited portfolio are conducting scientific research and clinical trials where the outcome is inherently uncertain and there is significant risk of negative results or adverse events arising. In addition, many companies in the Syncona Limited portfolio have yet to commercialise a product and their ability to do so may be affected by operational, commercial and other risk

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About Syncona

Syncona's purpose is to invest to extend and enhance human life. We do this by creating and building companies to deliver transformational treatments to patients in areas of high unmet need.

Our strategy is to create, build and scale companies around exceptional science to create a diversified portfolio of 20-25 globally leading healthcare businesses for the benefit of all our stakeholders. We focus on developing treatments for patients by working in close partnership with world-class academic founders and management teams. Our balance sheet underpins our strategy enabling us to take a long-term view as we look to improve the lives of patients with no or poor treatment options, build sustainable life science companies and deliver strong risk-adjusted returns to shareholders.

Autolus Therapeutics Presents Positive Results from Pivotal Phase 2 FELIX study in adult r/r B-ALL at ASCO

-     76% of patients treated with obe-cel in the FELIX study achieved a response (CR/CRi), primary endpoint has been met based on previously communicated interim analysis

-     Potential best in class tolerability, with very low levels of high-grade CRS and ICANS

-     Robust and reliable manufacturing and logistics, with 84% of enrolled patients receiving obe-cel

-     Analyst call to be held today, June 2, 2023 at 4.00 pm ET/9.00 pm BST

LONDON, June 2, 2023 -- Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, today announces the presentation of top-line data from the Pivotal Phase 2 FELIX study of obe-cel in adult r/r B-cell Acute Lymphoblastic Leukemia (B-ALL) at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

In the pivotal morphological cohort of the FELIX trial, 112 patients with r/r adult ALL were enrolled and 94 (84%) patients were dosed with obe-cel. Of the dosed patients, 76% patients achieved a complete response (CR) or CR with incomplete haematological recovery (CRi), and 97% of the responders with evaluable samples were in deep remission with no detectable minimal residual disease (MRD). Furthermore, at a 9.5-month median follow up, 61% of responders remained in ongoing remission without new anti-cancer therapies. CAR T cellular kinetics demonstrate excellent CAR T engraftment and persistence and are consistent with the prior ALLCAR19 study. 

Safety analysis demonstrated a potentially best-in-class tolerability profile with Grade ≥3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 3% (3/94) and 7% (7/94) of patients, respectively. Most of the toxicity was seen in patients with high disease burden. Notably, 6 of 7 Grade ≥3 ICANS were observed among patients with very high tumor burden of more than 75% bone marrow blasts at lymphodepletion. Overall, grade ≥3 adverse events occurred in 79% of patients, with neutropenia (36.2%), and thrombocytopenia (25.5%) most commonly reported. 

Manufacturing was reliable and consistent, with product released for 94% of leukapheresed patients and median turnaround times of 21 days from vein to release.

"We are very encouraged by the outcome of the FELIX study. Obe-cel shows low immunotoxicity, high complete remission rates and excellent CAR T expansion and persistence in adult B-ALL. These data are consistent with the prior ALLCAR19 study and suggest that obe-cel has the potential for long-term clinical benefit in adult B-ALL patients without additional therapies," said Dr. Claire Roddie, Associate Professor at UCL, Honorary Consultant Haematologist at UCLH. 

"We are pleased that our pivotal FELIX study confirms the attractive product profile for obe-cel, combining a high level of clinical activity with an excellent safety profile which we know is critical for this highly pre-treated and frail patient population. Conducting this study through the pandemic was a pressure test for obe-cel's product profile and our ability to deliver obe-cel reliably under difficult circumstances. We would like to thank patients, their care givers, nurses and treating physicians for their participation in the FELIX study." said Dr. Christian Itin, Chief Executive Officer of Autolus.

"With the Nucleus, our commercial manufacturing facility, well advanced in validation we look forward to submitting a BLA towards the end of this year and working with the FDA to get obe-cel to patients as soon as possible."

ASCO Oral Presentation, abstract #7000:

Title:    Safety and efficacy of Obecabtagene autoleucel (obe-cel, AUTO1), a fast-off rate CD19 CAR in relapsed/refractory adult B-Cell acute lymphoblastic leukemia (r/r B-ALL): Topline results of the pivotal FELIX study

Session Title:  Hematologic Malignancies - Leukemia, Myelodysplastic Syndromes, and Allotransplant

Session date and time: Friday, June 2, 2023, 2.00 pm -2.12 pm ET, 7.00 pm - 7.12 pm BST

Presenting Author: Dr. Claire Roddie, MD, PhD, FRCPath, Consultant Haematologist and Honorary Senior Lecturer, Cancer Institute, University College London (UCL)

Additional data from the FELIX study will be presented as an Oral Presentation at the upcoming European Hematology Association (EHA) meeting:

Title:    Safety and efficacy of Obecabtagene autoleucel (obe-cel, AUTO1), a fast-off rate CD19 CAR in relapsed/refractory adult B-Cell acute lymphoblastic leukemia (r/r B-ALL): Topline results of the pivotal FELIX study

Presentation ID: S262

Session date and time: Saturday, June 10, 2023, 11.00 am - 11.15 am ET, 4.00 pm - 4.15 pm BST

Presenting Author: Dr. Claire Roddie, MD, PhD, FRCPath, Consultant Haematologist and Honorary Senior Lecturer, Cancer Institute, University College London (UCL)

Conference Call

Autolus will host a conference call and webcast today for analysts at 4.00 pm ET/9.00 pm BST to summarize the ASCO data. 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.

A simultaneous audio webcast and replay will be accessible on the events section of Autolus' website.

About Autolus Therapeutics plc

Autolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the Company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information, please visit www.autolus.com.

About obe-cel (AUTO1)

Obe-cel is a CD19 CAR T cell investigational therapy designed to overcome the limitations in clinical activity and safety compared to current CD19 CAR T cell therapies. Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, obe-cel may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the ability of the programmed T cells to engage in serial killing of target cancer cells. In collaboration with Autolus' academic partner, UCL, obe-cel is currently being evaluated in a Phase 1 clinical trials for B-NHL. Autolus has progressed obe-cel to the FELIX trial, a pivotal trial for adult ALL.

About obe-cel FELIX clinical trial

Autolus' Phase 1b/2 clinical trial of obe-cel enrolled adult patients with relapsed / refractory B-precursor ALL. The trial had a Phase 1b component prior to proceeding to the single arm, Phase 2 clinical trial. The primary endpoint is overall response rate, and the secondary endpoints include duration of response, MRD negative CR rate and safety. The trial enrolled over 100 patients across 30 of the leading academic and non-academic centers in the United States, United Kingdom and Europe. [NCT04404660]

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding the expected benefits and continued development of Autolus' obe-cel program; the planned submission of a Biologics License Application for obe-cel by the end of 2023; and the Company's manufacturing capabilities, including the completion and validation of the Nucleus facility. Any forward-looking statements are based on management's current views and assumptions and involve risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in such statements. These risks and uncertainties include, but are not limited to, the risks that Autolus and Cardinal Health are unable agree on a definitive agreement, or that the arrangement described in such an agreement does not produce the desired results; Autolus' preclinical or clinical programs do not advance or result in approved products on a timely or cost effective basis or at all; the cost, timing, and results of clinical trials; that many product candidates do not become approved drugs on a timely or cost effective basis or at all. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Autolus' actual results to differ from those contained in the forward-looking statements, see the section titled "Risk Factors" in Autolus' Annual Report on Form 20-F filed with the Securities and Exchange Commission on March 7, 2023, as well as discussions of potential risks, uncertainties, and other important factors in Autolus' subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Autolus undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law.

Contact:

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