CELYAD (EBR:CYAD) Celyad Presents Update on CYAD-01 Solid Tumor Clinical Program at the SITC 33rd Annual Meeting

Transparency directive : regulatory news

09/11/2018 18:45

  • Standalone CYAD-01 without preconditioning leads to disease
    stabilization in three out of 11 metastatic colorectal cancer (mCRC)
    patients in THINK Phase 1 trial

  • Initial data from first dose cohort of SHRINK trial, evaluating
    CYAD-01 with FOLFOX in the neoadjuvant setting, shows three out of
    three mCRC patients with liver metastases achieved pathological
    objective clinical response, including one patient with a pathological
    complete response (pCR) and two patients with pathological partial
    response (pPR)

  • Preliminary safety data from THINK CyFlu cohort, evaluating CYAD-01
    with preconditioning, remains encouraging with improvement in CYAD-01

Regulatory News:

Celyad (Paris:CYAD) (Brussels:CYAD) (NASDAQ:CYAD), a clinical-stage
biopharmaceutical company focused on the development of CAR-T cell-based
therapies, today announced updated clinical results for the CYAD-01
program in solid tumors as well as translational research data presented
at the Society for Immunotherapy of Cancer (SITC) 33rd Annual

THINK Phase 1 Trial Update

  • Results from the dose-escalation trial were reported at SITC (abstract
    P255). Overall 14 patients with relapsed/refractory disease (11 mCRC,
    two ovarian and one pancreatic) were enrolled in the trial, evaluating
    CYAD-01 without preconditioning chemotherapy at three different dose
    levels (300 million, 1 billion and 3 billion cells per injection) of
    one cycle of three administrations with two-week intervals. Patients
    treated at the highest dose level presenting signs of clinical
    activity (stable disease or greater) were eligible to receive a second
    cycle of treatment.

  • Overall four patients experienced confirmed disease stabilization
    (three mCRC patients and one patient with ovarian cancer) according to
    RECIST 1.1 criteria.

  • As a monotherapy treatment, CYAD-01 was well tolerated. Nine grade 3/4
    treatment-related adverse events (AEs) were reported in five different
    patients including a grade 4 cytokine release syndrome (CRS) in dose
    level 3 considered as a dose-limiting toxicity (DLT). Five additional
    patients recruited at the same dose showed no further evidence of
    severe toxicity.

  • The peak level of peripheral CYAD-01 cells detected seem to correlate
    with the dose level and clinical response.

SHRINK Phase 1 Trial Update

  • The open-label, dose-escalation Phase 1 trial is assessing the safety
    and activity of CYAD-01 administered concurrently with FOLFOX
    chemotherapy in patients with liver metastases from colorectal cancer
    (CRC). Patients will receive six cycles of FOLFOX chemotherapy every
    two weeks and three administrations of CYAD-01 every two weeks 48
    hours after the end of chemotherapy at cycles two, three and four.
    Based upon initial assessment of clinical activity, patients could be
    eligible to receive three additional administrations of CYAD-01 at the
    same dose level.

  • To date, enrollment of dose level one (100 million cells per
    injection) has been completed with three metastatic treatment-naïve
    patients. All patients have undergone resection without delays in

  • Initial activity results assessed by pathological response criteria
    showed all three patients achieved an objective clinical response,
    including one patient with a pCR and two patients with pPR.

  • Concurrent treatment of CYAD-01 with FOLFOX chemotherapy appears to be
    well tolerated, with no occurrence of serious AEs (SAEs) nor increase
    of treatment-related AEs rate.

  • In addition, the expansion of peripheral CYAD-01 cells with a
    concurrent administration of FOLFOX chemotherapy is similar to the one
    observed with the standalone CYAD-01.

  • Full data from the SHRINK Phase 1 trial are expected in mid-2019.

THINK CyFlu Phase 1 Cohort Update

  • In February 2018, the THINK trial was amended to include a cohort
    known as THINK CyFlu (previously referred to as DEPLETHINK-CRC). The
    cohort evaluates a single injection of CYAD-01 following treatment
    with the standard preconditioning regimen of cyclophosphamide (300
    mg/m²) and fludarabine (30 mg/m²), or CyFlu. CyFlu is administered
    daily at days -5, -4 and -3 prior to treatment with CYAD-01.

  • To date, two patients have been enrolled into the cohort and completed
    the treatment schedule at the dose of 300 million cells per injection.
    Treatment with CYAD-01 following the standard preconditioning regimen
    of CyFlu was well tolerated with no occurrence of SAEs nor an increase
    of treatment-related AEs rate. As of November 9,
    the two enrolled patients were not yet evaluable for clinical response.

  • Preliminary translational data suggest an improvement in the cell
    expansion of CYAD-01 induced by the CyFlu preconditioning.

  • Full data from the THINK CyFlu Phase 1 cohort are expected in mid-2019.

Dr. Frédéric Lehmann, VP of Clinical Development & Medical Affairs at
Celyad, commented, “Solid tumors remain the greatest current
challenge for any T cell therapy. One of the major hurdles is the lack
of suitable targets, and in our perspective, NKG2D ligands that are
targeted by CYAD-01 represent an attractive family of targets on solid
tumors that may be exploited by our clinical candidates. I am encouraged
that to date CYAD-01 is well tolerated as a monotherapy for the
treatment of mCRC, while preliminary observations of clinical activity
in the form of disease stabilization imply that there is potential for
the approach. Furthermore, the initial findings of clinical activity
reported from the initial dose level of CYAD-01 when administered
concurrently with standard-of-care chemotherapy in the SHRINK trial are
encouraging and provide support for this view.”

Celyad also highlighted several updates to the broader solid tumor
development program and non-gene edited, allogeneic platforms.

LINK Phase 1 Trial Update

  • Following a strategic review of the CYAD-01 program in CRC, the
    Company has decided to stop enrollment of the LINK trial. The
    dose-escalation study had planned to assess the safety and clinical
    activity of multiple hepatic transarterial administrations of CYAD-01
    in patients with unresectable liver metastases from CRC. To date, one
    patient in dose level one has been enrolled in the study.

alloSHRINK Phase 1 Trial Update

  • In July 2018, the U.S. Food and Drug Administration (FDA) permitted
    the Investigational New Drug (IND) application for CYAD-101, the
    world’s first non-gene edited, allogeneic CAR-T clinical candidate, to
    go into effect. As previously announced, CYAD-101 will initially be
    evaluated in the alloSHRINK trial.

  • alloSHRINK is an open-label, dose-escalation trial that will assess
    the safety and clinical activity of CYAD-101 administered concurrently
    with FOLFOX chemotherapy in patients with unresectable mCRC. Similar
    to the SHRINK trial for CYAD-01, patients will receive six cycles of
    FOLFOX chemotherapy every two weeks and three administrations of
    CYAD-01 every two weeks 48 hours after the initiation of chemotherapy
    cycles one, two and three.

  • Enrollment in the trial is expected to begin by year-end 2018 with
    topline data anticipated during the second half of 2019.

Next-Generation, Allogeneic shRNA Platform

  • In October 2018, Celyad announced it had entered into an exclusive
    agreement with Horizon Discovery Group for the use of its shRNA
    technology to generate a novel, next-generation, non-gene-edited
    allogeneic platform. Initial results from preclinical studies
    demonstrating the versatility of the shRNA technology in the
    allogeneic setting will also be presented at SITC (abstract P220).
    Follow up data for the platform are expected in the first quarter of

“We are excited about the progress we have made thus far with our
solid tumor program for lead candidate CYAD-01,”
said David Gilham,
Ph.D., VP of Research and Development at Celyad. “We continue to
investigate complementary regimens for CYAD-01 for the treatment of
metastatic colorectal cancer that we believe may help to drive
additional clinical activity in this devastating disease where a true
unmet medical need exists. Additionally, CYAD-101 offers a
first-in-class investigational allogeneic CAR-T for the treatment of
mCRC and leverages our overall clinical experience within the indication
while strategically positioning the Company to be a leading player in
both the autologous and allogeneic CAR-T cell therapy space.”

SITC Analyst/Investor Event
Celyad will host an Analyst/Investor
event on Saturday, November 10, 2018, beginning at 12:30 p.m. ET to
review data presented at SITC. The company presentation for the event
will be available under Events & Webcasts in the Investors section of
the Company’s website.

Background on CYAD-01 and CYAD-101

CYAD-01 is an investigational, autologous CAR-T therapy in which a
patient's T cells are engineered to express the chimeric antigen
receptor NKG2D, a receptor expressed on natural killer (NK) cells that
binds to eight stress-induced ligands expressed on tumor cells. CYAD-101
is an investigational, non-gene edited, allogeneic (donor derived) CAR-T
therapy that co-expresses the company’s CYAD-01 CAR-T construct and the
novel inhibitory peptide TIM (T cell receptor [TCR] Inhibiting
Molecule). TCR signalling is responsible for Graft versus Host Disease
(GvHD). The expression of TIM reduces signalling of the TCR complex and
could therefore reduce or eliminate GvHD in patients treated with

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About Celyad

Celyad is a clinical-stage biopharmaceutical company focused on the
development of specialized CAR-T cell-based therapies. Celyad utilizes
its expertise in cell engineering to target cancer. Celyad’s CAR-T cell
platform has the potential to treat a broad range of solid and
hematologic tumors. Its lead oncology candidate, CYAD-01 (CAR-T NKG2D),
is currently being evaluated in a Phase I dose escalation clinical trial
to assess the safety and clinical activity of multiple administrations
of autologous CYAD-01 cells in seven refractory cancers including five
solid tumors (colorectal, ovarian, bladder, triple-negative breast and
pancreatic cancers) and two hematological tumors (acute myeloid leukemia
and multiple myeloma). The safety and clinical activity of the CYAD-01
therapy concurrently administered with standard-of-care treatments or
preconditioning chemotherapy is also being assessed in a full clinical
development program focused on acute myeloid leukemia and colorectal
cancer. Celyad was founded in 2007 and is based in Mont-Saint-Guibert,
Belgium, and New York, NY. Celyad’s ordinary shares are listed on the
Euronext Brussels and Euronext Paris exchanges, and its American
Depository Shares are listed on the Nasdaq Global Market, all under the
ticker symbol CYAD.

Forward-looking statements

This release may contain forward-looking statements, including
statements regarding the safety and efficacy of CYAD-01 and CYAD-101;
statements concerning the ongoing and planned clinical development of
CYAD-01 and CYAD-101, including the timing of trials, enrollment, data
readouts and presentations; the clinical and commercial potential of
CYAD-01 and CYAD-101 and the adequacy of Celyad’s financial resources;
statements concerning Celyad’s exclusive agreement with Horizon
Discovery Group; the clinical and commercial potential of its shRNA
technology; Celyad’s financial condition, results of operation and
business outlook; and Celyad’s expected cash burn. Forward-looking
statements may involve known and unknown risks, uncertainties and other
factors which might cause actual results, financial condition and
liquidity, performance or achievements of Celyad, or industry results,
to differ materially from those expressed or implied by such
forward-looking statements. In particular it should be noted that the
data summarized above are preliminary in nature. There is limited data
concerning safety and clinical activity following treatment with the
CYAD-01 and CYAD-101 drug product candidates. These results may not be
repeated or observed in ongoing or future studies involving the CYAD-01
and CYAD-101 drug product candidates. These forward-looking statements
are further qualified by important factors and risks, which could cause
actual results to differ materially from those in the forward-looking
statements, including statements about: the initiation, timing, progress
and results of our preclinical studies and clinical trials, and our
research and development programs; our ability to advance drug product
candidates into, and successfully complete, clinical trials; our ability
to successfully manufacture drug product for our clinical trials,
including with our mAb manufacturing process and with respect to
manufacturing drug product with the desired number of T cells under our
clinical trial protocols; our reliance on the success of our drug
product candidates, including our dependence on the regulatory approval
of CYAD-01 and CYAD-101 in the United States and Europe and subsequent
commercial success of CYAD-01 and CYAD-101, both of which may never
occur; the timing or likelihood of regulatory filings and approvals; our
ability to develop sales and marketing capabilities; the
commercialization of our drug product candidates, if approved; the
pricing and reimbursement of our drug product candidates, if approved;
the implementation of our business model, strategic plans for our
business, drug product candidates and technology; the scope of
protection we are able to establish and maintain for intellectual
property rights covering our drug product candidates and technology; our
ability to operate our business without infringing, misappropriating or
otherwise violating the intellectual property rights and proprietary
technology of third parties; cost associated with enforcing or defending
intellectual property infringement, misappropriation or violation;
product liability; and other claims; regulatory development in the
United States, the European Union, and other jurisdictions; estimates of
our expenses, future revenues, capital requirements and our needs for
additional financing; the potential benefits of strategic collaboration
agreements and our ability to maintain and enter into strategic
arrangements; our ability to maintain and establish collaborations or
obtain additional grant funding; the rate and degree of market
acceptance of our drug product candidates, if approved; our financial
performance; developments relating to our competitors and our industry,
including competing therapies and statements regarding future revenue,
hiring plans, expenses, capital expenditures, capital requirements and
share performance. A further list and description of these risks,
uncertainties and other risks can be found in Celyad’s U.S. Securities
and Exchange Commission (SEC) filings and reports, including in its
Annual Report on Form 20-F filed with the SEC on April 6, 2018 and
subsequent filings and reports by Celyad. Given these uncertainties, the
reader is advised not to place any undue reliance on such
forward-looking statements. These forward-looking statements speak only
as of the date of publication of this document and Celyad’s actual
results may differ materially from those expressed or implied by these
forward-looking statements. Celyad expressly disclaims any obligation to
update any such forward-looking statements in this document to reflect
any change in its expectations with regard thereto or any change in
events, conditions or circumstances on which any such statement is
based, unless required by law or regulation.


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