REG - Syncona Limited - Autolus presents clinical data updates

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11/12/2023 07:15

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RNS Number : 3130W  Syncona Limited  11 December 2023

 

 

 

Syncona Limited

 

Autolus presents clinical data updates

 

11 December 2023

 

Syncona Ltd, a leading healthcare company focused on creating, building and
scaling a portfolio of global leaders in life science, notes that its
portfolio company, Autolus Therapeutics Plc (Nasdaq: AUTL) ("Autolus"), has
presented clinical data updates, including from its pivotal Phase II FELIX
study of obe-cel in adult r/r B-cell acute lymphoblastic leukaemia (B-ALL), at
the 2023 American Society of Hematology (ASH) Annual Meeting.

 

Highlights from the presentations include:

 

·      Pooled analysis from the pivotal FELIX study of obe-cel in adult
ALL shows the therapy has a differentiated safety profile with very low rates
of severe toxicity, as well as continued high response rates and prolonged
event free survival.

·      The observed response rate 1  (#_ftn1) of 78% in evaluable
patients amongst the 127 patients dosed in the study at a median follow up of
16.6 months continues to be consistent with previously presented data.

·      Longer-term follow-up data from a pooled analysis from the
pivotal FELIX and academic ALLCAR19 studies show durable remissions amongst a
subset of patients after a median follow-up of > three years.

·      Data from the Phase I ALLCAR19 extension study in B-cell
non-Hodgkin lymphoma (B-NHL) and chronic lymphocytic leukemia (B-CLL) also
show the strong durability and safety profile of obe-cel in other B-cell
malignancies.

·      Initial data from the MCARTY Phase I study of AUTO8, Autolus'
next generation product candidate targeting multiple myeloma, show the therapy
was well tolerated with responses observed in all patients.

 

Autolus recently announced that it has submitted its Biologics License
Application (BLA) to the US Food and Drug Administration (FDA) for obe-cel in
r/r adult ALL and plans to file a Marketing Authorisation Application with the
European Medicines Agency (EMA) in the first half of CY2024.

 

Martin Murphy, Director on the Board of Autolus Therapeutics, said: "The
updated data from the FELIX study of obe-cel further underline the strong
safety profile of the drug and importantly show a durable response for
patients. The FELIX study is one of the largest CAR-T cell studies in adults
with r/r B-ALL and I am pleased to see the continued data supporting our
belief that obe-cel has the potential to transform the lives of patients with
ALL."

 

The announcement can be accessed on Autolus' investor website
at https://www.autolus.com/investor-relations/news/
(https://www.autolus.com/investor-relations/news/)  and the full text of the
announcement from Autolus is contained below.

 

 ENDS 

 

Enquiries

 

Syncona Ltd

 

Annabel Clark / Fergus Witt

Tel: +44 (0) 20 3981 7940

 

FTI Consulting

 

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Tel: +44 (0) 20 3727 1000

 

 

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, across development stage and therapeutic areas, 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.

 

Syncona Limited seeks to achieve returns over the long term. Investors should
seek to ensure they understand the risks and opportunities of an investment in
Syncona Limited, including the information in our published documentation,
before investing.

 

 

 

Autolus Therapeutics Presents Clinical Data Updates at the American Society of
Hematology (ASH) Annual Meeting 2023

 

-     Pooled analysis of the FELIX Phase Ib/II study 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

 

-     Longer-term data from a pooled analysis from the ALLCAR19 study and
FELIX Phase Ib 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

 

-     Additionally, ALLCAR19 extension cohorts demonstrated long-term
responses with low immunotoxicity and prolonged persistence in patients with
aggressive and indolent r/r NHL and r/r CLL

 

-     Initial data from the MCARTY Phase I study in multiple myeloma
showed AUTO8 was well tolerated, with responses observed in all patients

 

-     Autolus will host an in-person and webcast Analyst/Investor event to
discuss the data on Sunday, December 10, 2023 at 8:00 AM PT / 4.00 PM GMT

 

LONDON, December 9, 2023 -- Autolus Therapeutics plc (Nasdaq: AUTL), a
clinical-stage biopharmaceutical company developing next-generation programmed
T cell therapies, announces two oral presentations and two poster
presentations at the American Society of Hematology (ASH) Annual Meeting,
December 9-12, 2023, including an oral presentation highlighting data from a
pooled analysis of the FELIX Phase Ib/II study of obe-cel, an autologous fast
off-rate CD19 CAR T therapy, in relapsed/refractory adult B-ALL; and as a
poster presentation a long-term update on the pooled ALLCAR19 and FELIX phase
1b studies, evaluating obe-cel in adult patients with r/r B-ALL as well from
the ALLCAR19 study patients with B-NHL and B-CLL. Finally, in an oral
presentation pre-clinical and Phase I clinical data from AUTO8, a BCMA/CD19
co-targeting CAR T cell candidate, evaluated in patients with refractory
multiple myeloma.

 

"The FELIX study, with 127 patients, is one of the largest CAR T cell studies
in adults with r/r B-ALL. Obe-cel had a favorable safety profile with very low
rates of severe CRS and ICANS, in a clinical setting where these toxicities
tend to be frequent and severe. A high proportion of patients responded, with
many responses sustained, particularly in patients with low or intermediate
disease-burden at lymphodepletion. The FELIX study shows that obe-cel has the
potential to become an important therapeutic option in adults with r/r B-ALL."
said Dr. Claire Roddie, MD, PhD, FRCPath, Associate Professor Haematology and
Honorary Consultant Haematologist, Cancer Institute, University College London
(UCL).

 

"The data we are sharing at ASH from our prior studies indicate that a subset
of relapsed and refractory adult ALL patients treated with obe-cel as a single
agent continue in remission with a median follow-up of more than three years.
It is gratifying to see the excellent safety profile, high response rate and
event-free survival we observed in our prior studies, reproduced in the FELIX
study," said Dr. Christian Itin, Chief Executive Officer of Autolus. "We have
recently submitted a Biologics License Application (BLA) for obe-cel to the
U.S. Food and Drug Administration (FDA) for the treatment of patients with
relapsed/refractory (r/r) adult B-cell Acute Lymphoblastic Leukemia (ALL) and
we look forward to working with the FDA through the regulatory approval
process."

 

Abstract #222 - oral presentation:

 

Title: Obecabtagene Autoleucel (obe-cel, AUTO1) for Relapsed/Refractory Adult
B-cell          Acute Lymphoblastic Leukemia (R/R B-ALL): Pooled
Analysis of the Ongoing FELIX Phase Ib/II Study

Link to Presentation
(https://www.autolus.com/media/4xbmrn5p/cr_roddie-et-al_felix-pooled-analysis_oral-presentation_ash23_final2-1dec23.pdf)
(https://www.autolus.com/media/4xbmrn5p/cr_roddie-et-al_felix-pooled-analysis_oral-presentation_ash23_final2-1dec23.pdf)
 
(https://www.autolus.com/media/4xbmrn5p/cr_roddie-et-al_felix-pooled-analysis_oral-presentation_ash23_final2-1dec23.pdf)

Session Title: 704. Cellular Immunotherapies: Early Phase and Investigational
Therapies: Expanding Disease Targets for CAR-T Cell Therapies

Session date and time: Saturday, December 9, 2023, 3:15 PM PT

Session room: San Diego Convention Center, Room 6B

Publication Number:  222

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

 

Summary:

Obe-cel is an autologous chimeric antigen receptor T cell product using a fast
off-rate CD19 binding domain designed to reduce toxicity and increase
long-term persistence. A pooled analysis of data from all patients across all
cohorts in the FELIX Phase Ib/II study (morphologic disease, minimal residual
disease (MRD), isolated extramedullary disease (EMD)) were presented (n=127,
median follow-up time from first obe-cel infusion to data cut-off of 16.6
months). Median vein-to-release time was 22 days. Across all patients,
treatment with obe-cel resulted in a high response rate with CR/CRi rate of
78% in evaluable patients. Additionally, obe-cel showed a favorable safety
profile; grade ≥3 CRS was 2% and grade ≥3 ICANS was 7%, with most severe
cases of immunotoxicity occurring in patients with high leukemic burden in the
bone marrow (BM). The event free survival estimate (EFS) at 12-months was 50%
across all patients, with only 17% of responders proceeding to stem cell
transplant while in remission.  For patients who had morphologic disease,
defined as ≥5% BM blasts or presence of EMD regardless of BM blast status,
at lymphodepletion, 74% responded with CR or CRi, and 95% of evaluated
responders were MRD-negative‡. For patients who did not have morphologic
disease at lymphodepletion, 100% were MRD-negative§ after obe-cel infusion.
Subgroup analysis demonstrated that EFS and safety, particularly rate of CRS
and ICANS, were better in patients with lower disease burden at
lymphodepletion (see table below).  Cellular kinetic data shows high
expansion and long-term persistence of CAR T cells in most responders.

 

Table: Summary EFS and safety by bone-marrow blasts prior to lymphodepletion

               Overall   <5% BM blasts     5−75% BM blasts    >75% BM blasts

               (n=127)   (n = 36)          (n = 51)           (n = 40)
 12-month EFS  50%       65%               55%                27%
 ≥G3 CRS       2%        0%                4%                 3%
 ≥G3 ICANS     7%        0%                6%                 15%

 

Event free survival (EFS; the time from date of first infusion to the earliest
of treatment failure, relapse, or death from any cause); measurable residual
disease (MRD); Bone marrow (BM); Extramedullary disease (EMD); complete
remission (CR); Complete remission with incomplete count recovery (CRi); ‡
MRD status available for 64/73 patients; § MRD status available for 27/29
patients.

 

Abstract #350 - oral presentation

Title: Development of a Phase I Study Evaluating the Activity of Modular CAR T
for Multiple Myeloma (MCARTY) Targeting BCMA and CD19 for Improved
Persistence

Link to Presentation
(https://www.autolus.com/media/yuolbxcz/lee_et_al_ash2023_mcarty_study_v0-06_final.pdf)
 
(https://www.autolus.com/media/yuolbxcz/lee_et_al_ash2023_mcarty_study_v0-06_final.pdf)

Session Title: 703. Cellular Immunotherapies: Basic and Translational:
Cellular Immunotherapy: Preclinical and Translational Insights

Date and time: Saturday, December 9, 2023, 4:15 PM PT

Session room: San Diego Convention Center, Room 6A

Publication Number:  350

Presenting Author: Dr. Lydia Lee, Consultant Haematologist & Senior
Clinical Research             Fellow, University College London,
Research Department of Haematology (UCLH).

 

Summary:

AUTO8 is a dual targeting autologous CAR T therapy targeting BCMA and CD19
using two independently expressed CARs (D8 BCMA CAR and AUTO1/obe-cel CAR
respectively) for R/R multiple myeloma. The MCARTY study is an iterative,
staggered design trial with two separate parallel cohorts for direct
comparison of D8 BCMA CAR and AUTO8.  As of November 13, 2023 (data cut-off),
11 patients have been infused with either BCMA CAR at 50 million (n=3) or 150
million (n=3) cells, or AUTO8 at 50 million (n=3) or 150 million (n=2). At a
median follow-up of 6 months we observed 100% response rate (ORR), with 3 PR,
1 VGPR, 7 CR/sCR (all evaluable MRD negative). Two patients remained in
ongoing sCR > 12 months. No cases of ICANS or CRS ≥ Gr 3 were observed
across all subjects during the period.  While persistence data from the dual
targeting cohort is immature, it demonstrates expansion of three CAR
populations and suggests a trend to increased persistence of D8 BCMA CAR
expressing T cells. The MCARTY trial is ongoing and continues to recruit
patients.

 

Poster Presentations:

 

Title: Long-Term Efficacy and Safety of Obecabtagene Autoleucel (obe-cel) in
Adult Patients (pts) with Relapsed/Refractory B-cell Acute Lymphoblastic
Leukemia ([R/R B-       ALL]; Pooled Analysis from ALLCAR19 and FELIX
Phase Ib Studies) or Other B-cell Malignancies (ALLCAR19 Extension Study)

Link to Poster
(https://www.autolus.com/media/pujlzxym/ash-2023-allcar-felix-roddie-2114_poster.pdf)
 
(https://www.autolus.com/media/pujlzxym/ash-2023-allcar-felix-roddie-2114_poster.pdf)

Session Title: 704. Cellular Immunotherapies: Early Phase and Investigational
Therapies: Poster Session date and time: Saturday, December 9, 2023, 5:30 PM -
7:30 PM PT

Session room: San Diego Convention Center, Halls G-H

Publication Number:  2114

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

 

Summary:

The clinical activity of obe-cel has been explored in adults with R/R B-ALL in
a Phase I study (ALLCAR19), and a Phase Ib/II study (FELIX). Additionally,
obe-cel has been tested in patients with R/R B-cell chronic lymphocytic
leukemia (B-CLL) and R/R B-cell non-Hodgkin lymphoma (B-NHL). Data from the
pooled analysis of r/r ALL patients (n=36) treated with obe-cel in the
ALLCAR19 and FELIX Ib studies demonstrate high remission rates of 81% (29/36).
After a median follow-up of 3 years and without subsequent transplant 41% of
patients continue in complete remission. The estimated EFS rate with censoring
of subsequent transplant or new treatment was 45% at 36 months; all patients
in ongoing remission were MRD negative at last assessment and median duration
of response was not reached. In the CLL and NHL cohorts of the ALLCAR19 study
and with >2 years follow up, high response rates and durable responses were
observed. Low grade or low frequency grade >3 CRS/ICANS was observed across
all indications and all dosing regimens. Excellent expansion and persistence
of CAR T cells was evident across the studies. In summary, obe-cel shows
durable remissions in a range of B-cell malignancies with a consistent safety
profile.

 

Title: Delivery of Obecabtagene Autoleucel (obe-cel, AUTO1) for the FELIX
Pivotal Study Demonstrating Robust Cell Processing, Robust Release Testing,
and Reliable Logistics, Together with Readiness for Sustainable Patient (pt)
Care

Session Title: 711. Cell Collection and Processing: Poster III

Session date and time: Monday, December 11, 2023, 6:00 PM - 8:00 PM PT

Session room: San Diego Convention Center, Halls G-H

Publication Number:  4892

Presenting Author: Michael Merges VP, Process Development, Autolus

 

Analyst/Investor Event:

 

Date: Sunday, December 10, 2023

Time: The presentation will be from 8:00 AM PT / 4:00 PM GMT to 9:00 AM PT /
5:00 PM GMT. Onsite access to the event available from 7:45am PT

Venue: The Manchester Grand Hyatt, 1 Market Place, San Diego, CA 92101

Speakers: Dr. Claire Roddie, MD, PhD, FRCPath, Associate Professor Haematology
and Honorary Consultant Haematologist, Cancer Institute, University College
London (UCL); Dr. Christian Itin, Chief Executive Officer, Autolus.

Webcast Registration: A live webcast will be held alongside the event. To
register for the webcast please follow this link
(https://us06web.zoom.us/webinar/register/WN_5II55aO2Qbm8UIIm0hS1-Q) .

 

A recording of the event together with the presentation materials will be
available on the Company's website after the event.

 

Note that due to the ASH embargo policy details specific to Publication 4892
will not be included in the Analyst/Investor event.

 

About Autolus Therapeutics plc

Autolus is a clinical-stage biopharmaceutical company developing
next-generation, programmed T cell therapies for the treatment of cancer and
autoimmune disease. 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 target 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, solid tumors and autoimmune
diseases. 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. Obe-cel is designed with a fast target binding off-rate to
minimize excessive activation of the programmed T cells. Clinical trials of
obe-cel have demonstrated that this "fast off-rate" profile reduces toxicity
and T cell exhaustion, resulting in improved persistence and leading to high
levels of durable remissions in r/r Adult ALL patients. Autolus has filed a
BLA with the FDA for obe-cel in relapsed/refractory adult B-ALL and is
preparing a regulatory submission with EMA. In collaboration with Autolus'
academic partner, UCL, obe-cel is currently being evaluated in a Phase I
clinical trials for B-NHL.

 

About obe-cel FELIX clinical trial

Autolus' Phase Ib/2 clinical trial of obe-cel enrolled adult patients with
relapsed / refractory B-precursor ALL. The trial had a Phase Ib 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 

 

About AUTO8

AUTO8 is our next-generation product candidate for multiple myeloma which
comprises two independent CARs for the multiple myeloma targets, BCMA and
CD19. We have developed an optimized BCMA CAR which is designed for improved
killing of target cell that express BCMA at low levels. This has been combined
with fast off rate CD19 CAR from obe-cel. We believe that the design of AUTO8
has the potential to induce deep and durable responses and extend the
durability of effect over other BCMA CARs currently in development.

 

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 development of
Autolus' product candidates, the status of clinical trials (including, without
limitation, expectations regarding the data that is being presented, the
expected timing of data releases and development, as well as completion of
clinical trials) and development timelines for the Company's product
candidates. 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' preclinical or
clinical programs do not advance or result in approved products on a timely or
cost effective basis or at all; the results of early clinical trials are not
always being predictive of future results; 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; the ability to enroll patients in
clinical trials; and possible safety and efficacy concerns. 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:

 

Julia Wilson

+44 (0) 7818 430877

j.wilson@autolus.com (mailto:j.wilson@autolus.com)

 

Susan A. Noonan

S.A. Noonan Communications

+1-917-513-5303

susan@sanoonan.com (mailto:susan@sanoonan.com)

 

Lauren Williams

Investase

+44 23 9438 7760

lauren@investase.com (mailto:lauren@investase.com)

 

 

 

# # #

 

 

 

 1  (#_ftnref1) Complete response / CR with incomplete haematological recovery

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