Planegg/Martinsried, June 27, 2024.
Medigene AG (Medigene or the “Company”, FSE: MDG1, Prime Standard),
an immuno-oncology platform company focusing on the discovery and
development of T cell immunotherapies for solid tumors, today
provides a detailed overview of its lead candidate MDG1015, a
first-in-class 3rd generation T cell receptor engineered T cell
(TCR-T) therapy, at the 7th Cell and Gene Therapy In-Depth Focus
Summit from June 27-28, 2024, in Beijing, China. MDG1015 advances
towards the clinic and targets the cancer-testisantigens (CTA)
NY-ESO-1 / LAGE-1a (New York esophageal squamous cell carcinoma 1 /
L Antigen Family Member-1a) and is armored and enhanced by the
Company’s PD1-41BB costimulatory switch protein (CSP).
The presentation with the title “MDG1015: a 3rd
Generation TCR-T Therapy Incorporating the PD1-41BB Costimulatory
Switch Protein, Advancing to the Clinic” is available on Medigene’s
website: https://medigene.com/science/abstracts/
"Targeting tumors expressing CTAs has shown
promising clinical benefits, yet there remains a need to enhance
efficacy, safety, and response durability not only in orphan
indications but also in more common solid tumor types. We tackle
these issues with a comprehensive strategy, starting with the
development of a best-in-class TCR that is sensitive, specific, and
safe (3S TCR). Further, our innovative approach not only armors and
enhances the TCR-T cell functionality by combining our 3S TCRs with
the PD1-41BB CSP but also places a significant emphasis on the drug
product (DP) manufacturing process. This process is vital for
producing effective, safe, and durable TCR-T therapies" stated
Kirsty Crame, MD, VP Clinical Strategy & Development.
"Our focus on optimizing the DP composition is
intended to shorten the ex-vivo manufacturing time, thereby
reducing the overall vein-to-vein duration for patients. This will
be achieved while upholding the highest standards of safety,
efficacy, and durability."
A benefit of adding the PD1-41BB CSP to the
Company´s 3S TCRs has been shown in multiple in vitro assays
displaying elevated TCR-T cell proliferation, superior TCR-T cell
functionality as well as quick and consistent elimination of tumor
cells when compared to TCR-T cells lacking the CSP. It has been
demonstrated this effect is “”gated” in that the enhancement occurs
only after the 3S TCR binds to its specific target antigen.
This is an important safety feature of Medigene’s 3rd generation
TCR-T programs.In addition, Medigene devised an efficient 6-day
manufacturing process that emphasizes enriching CD8+ T cells while
preserving their stem-like properties. Research studies indicates
that DPs with more stem-like characteristics demonstrate increased
effectiveness and longer-lasting responses. By incorporating the
PD1-41BB CSP, the necessity for CD4+ T cells within the DP is
eliminated, allowing CD8+ T cells to independently produce the
necessary cytokines that would have been provided by the CD4+
cells. This approach mitigates potential risks associated with CD4+
T cells, potentially enhancing both the safety and therapeutic
benefits of the treatment.
Medigene's lead TCR-T program, MDG1015, is
scheduled for IND submission in the third quarter of 2024 and CTA
submission in the fourth quarter of 2024. MDG1015's clinical
indications were selected due to significant unmet medical needs,
the presence of the target antigen, and/or PD-L1 expression. This
decision resulted in the initial focus on evaluating gastric
cancer, ovarian cancer, myxoid/round cell liposarcoma, and synovial
sarcoma. Subject to additional financing, the first patient
enrollment is anticipated by the end of 2024. Based on this
timeline, the Company aims to unveil early data from the dose
escalation phase in the fourth quarter of 2025.
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About Medigene AG
Medigene AG (FSE: MDG1) is an immuno-oncology
platform company dedicated to developing differentiated T cell
therapies for treatment of solid tumors. Its End-to-End Platform is
built on multiple proprietary and exclusive technologies that
enable the Company to generate optimal T cell receptors against
both cancer testis antigens and neoantigens, armor and enhance
these T cell receptor engineered (TCR) -T cells to create
best-in-class, differentiated TCR-T therapies, and optimize the
drug product composition for safety, efficacy and durability. The
End-to-End Platform provides product candidates for both its own
therapeutics pipeline and partnering. Medigene’s lead TCR-T program
MDG1015 is on track for IND filing in Q3 2024 and CTA filing in Q4
2024. For more information, please visit https://medigene.com/
About Medigene’s MDG1015 Program
MDG1015 is a first-in-class, 3rd generation T
cell receptor engineered T cell (TCR-T) therapy targeting NY-ESO-1
/ LAGE-1a, a well-recognized and validated cancer testis antigen,
which is expressed in multiple tumor types. MDG1015 contains our
optimal affinity 3S (sensitive, specific and safe) NY-ESO-1
/LAGE-1a TCR combined with our proprietary PD1-41BB costimulatory
switch protein that blocks the PD1/PD-L1 inhibitory axis while
simultaneously activating the T cell through the well described
-41BB pathway further enhancing the activity and persistence of the
TCR-T cell in the hostile tumor microenvironment (TME). MDG1015 is
currently undergoing IND/CTA enabling studies with IND approval
expected in Q3 2024 and CTA approval in Q4 2024.
About Medigene’s PD1-41BB Costimulatory
Switch Protein
Checkpoint inhibition via PD-1/PD-L1
pathway:
Cells of solid tumors are sensitive to killing
by activated T cells but can escape this killing activity by
producing inhibitory molecules known as ‘checkpoint proteins’, such
as the Programmed Death Ligand 1 (PD-L1), on their surface. When
this occurs, activated T cells, which express PD-1, the natural
receptor for PD-L1, are inactivated. The expression of PD-L1 is an
adaptive immune resistance mechanism for tumors that can help them
survive and grow.
The 4-1BB (CD137) costimulatory signaling
pathway:
Effective T cell immune responses to antigens
typically require both a primary antigenic stimulation via the T
cell receptor (TCR) and costimulatory signals. The intracellular
signaling domains of the 4-1BB protein offer a well-characterized
pathway to costimulation and enhanced T cell responses.
Medigene’s PD1-41BB switch receptor turns the
tumor’s attempted self-defense mechanism against the tumor by
substituting the inhibitory signaling domain of PD-1 with the
activating signaling domain of 4-1BB. Therefore, instead of
inactivating T cells, the switch receptor delivers an activating
signal to TCR-T cells. PD1-41BB-modified TCR-T cells proliferate
strongly in the presence of PD-L1-positive tumor cells and kill
more tumor cells upon repeated exposure. Additionally, switch
receptor signals enable TCR-T cells to function better with low
levels of glucose or high levels of TGFß, two conditions
characteristic of strongly hostile tumor microenvironments.
This press release contains forward-looking
statements representing the opinion of Medigene as of the date of
this release. The actual results achieved by Medigene may differ
significantly from the forward-looking statements made herein.
Medigene is not bound to update any of these forward-looking
statements. Medigene® is a registered trademark of Medigene AG.
This trademark may be owned or licensed in select locations
only.
Medigene AG
Pamela Keck Phone: +49 89 2000 3333 01 E-mail:
investor@medigene.com
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