Codiak BioSciences, Inc. (Nasdaq: CDAK), a clinical-stage
biopharmaceutical company pioneering the development of
exosome-based therapeutics as a new class of medicines, today
announced platform-validating clinical data from Phase 1 trials of
exoSTINGTM and exoIL-12™ and plans to advance both candidates into
Phase 2 trials. In an open-label Phase 1 trial, exoIL-12
demonstrated a differentiating favorable safety and tolerability
profile, with no detectable systemic exposure of IL-12 and no
treatment-related adverse events, which has not previously been
reported by others with recombinant IL-12. The two patients with
cutaneous T cell lymphoma (CTCL) who have been treated each
received multiple (>20) injections of exoIL-12 and experienced
tumor regressions in both injected and non-injected lesions,
including a partial response in one patient. In the open-label
Phase 1/2 clinical trial evaluating exoSTING as a single agent in
patients with late-stage refractory solid tumors, data across all
five dose cohorts showed repeat doses of exoSTING were
well-tolerated, demonstrated tumor retention with no systemic
exposure of the STING agonist, and in a subset of patients, tumor
shrinkage was observed in injected and uninjected
lesions.
“We believe these positive datasets from our two
lead programs provide further clinical validation of our engEx®
Platform and the target profile for our engineered exosome
therapeutic candidates. In the studies, we were able to deliver
exoSTING and exoIL-12, with repeat dosing, to the tumor with a high
level of specificity, no observed systemic exposure or associated
toxicity, and an enhanced therapeutic index–while demonstrating
tumor shrinkage in both injected and uninjected lesions,” said
Douglas E. Williams, Ph.D., President and Chief Executive Officer
of Codiak. “STING and IL-12 have been challenging targets that have
historically been hampered by very toxic side effects, but we
believe our approach may enable best-in-class therapies with
favorable safety profiles. Based on these findings, we have
identified a recommended Phase 2 dose for both programs. We plan to
initiate a Phase 2 study of exoSTING in bladder cancer and a Phase
2 study of exoIL-12 in an expanded group of tumor types in the
first quarter of 2023.”
exoIL-12 Data and Development Plan
The Phase 1 clinical trial was designed in two
parts, with the data from the healthy volunteer portion of the
study reported last year. In the CTCL portion of the study, two
patients with early stage CTCL whose disease progressed on prior
therapy have been treated as of the June 10, 2022, data cut-off.
Each patient has received more than 20 injections of exoIL-12 (6.0
μg) across multiple lesions. Duration of treatment has been greater
than six months, and no treatment-related adverse events Grade 3 or
higher or SAEs were observed, and no dose modifications were
required.
exoIL-12 demonstrated improvement in overall tumor
burden, as measured by mSWAT, and lesion severity, as measured by
CAILS, in both patients treated. Patient 001 had a total of 5 skin
lesions, 3 of which were injected and exhibited a partial response,
as per mSWAT (a registrational endpoint) with a 61% decrease in
disease burden. Improvement in CAILS scores for all skin lesions,
both injected and uninjected, ranged from 20-80%. All skin lesions
have resolved, and additional injections were deemed unnecessary by
the treating physician. The patient remains on study. Patient 002
had 3 skin lesions, 2 of which were injected (20 injections to
date) and has demonstrated a 43% decrease in disease burden.
Improvement in CAILS scores have been seen ranging from 30-50% for
all lesions, both injected and uninjected. This patient remains on
study and continues to receive exoIL-12 injections.
Plasma pharmacokinetic (PK) measurements of both
healthy volunteers and patients that received exoIL-12 showed no
systemic exposure with levels of IL-12 below the limit of
quantification. In contrast, previous rIL-12 clinical studies
showed dose-dependent systemic exposure with dosages of 5 and 12 μg
resulting in Cmax plasma levels of approximately 15 to 45 pg/ml
within 6 to 12 hours after dosing.1
Data from the CTCL patients further validate 6
mcg as the intended dose for Phase 2 development. Codiak intends to
conclude the current study in the UK and transition to a U.S.
Investigational New Drug (IND) application. Codiak anticipates
initiating a Phase 2 trial during the first quarter of 2023 in
patients with cutaneous malignancies responsive to rIL-12 in
studies historically, including CTCL, Kaposi’s sarcoma, Merkel cell
carcinoma, and squamous cell carcinoma – each orphan cutaneous
diseases treated by the same physicians, where local treatment is
common.
exoSTING Data and Development Plan
Data as of June 10, 2022, are being reported
from all five escalation dose cohorts (0.3 mcg, 1.0 mcg, 3.0 mcg,
6.0 mcg and 12.0 mcg) enrolled in the Phase 1/2 study. Dosing is
still underway in the 12.0 mcg cohort and all patients continue to
be followed. Trial participants (n=23) were administered exoSTING
intratumorally, and nearly all had received at least two prior
therapies prior to study entry with most (65%) having progressed on
checkpoint inhibitors.
Plasma pharmacokinetic (PK) measurements of
patients that received exoSTING showed no systemic exposure to the
agonist. Further, analyses of available plasma biomarkers indicated
a lack of systemic inflammatory cytokines detectable in blood after
exoSTING administration.
Within all dose cohorts, exoSTING was
well-tolerated and no dose limiting toxicities or
treatment-emergent adverse events of Grade 3 or higher were
observed. Treatment-related serious adverse events (TRSAE) were
observed in three patients (2 patients with Grade 2 cytokine
release syndrome and 1 patient with Grade 1 pyrexia). All patients
who experienced a TRSAE were retreated and remained on study
without additional SAEs.
Blood biomarker assessments conducted post dosing
demonstrated dose-dependent activation of the STING pathway at
doses 100-fold lower in comparison to other free STING agonists.
Paired tumor biopsies available from Cohorts 1-4 show evidence of
an adaptive immune response, including consistent increases in CD-8
effector T-cells and PD-L1 in the tumor micro-environment.
Signs of antitumor activity were observed with
tumor shrinkage in injected as well as distal, non-injected
tumors.
The data support advancing exoSTING into Phase 2
development, particularly in early-stage disease where combination
with immunotherapy may lead to enhanced activity. Codiak has
identified 12.0 mcg as the intended dose for intratumoral
administration and plans to file a protocol amendment with FDA
later this year to enable initiation of a Phase 2 trial of exoSTING
in patients with bladder cancer (Muscle Invasive Bladder Cancer or
MIBC) during the first quarter of 2023.
“This is a critical milestone for Codiak because we
met our objectives for the Phase 1 studies of exoSTING and exoIL-12
and the data support the differentiated target profile we had hoped
to unlock with our engineered exosome platform. What is remarkable
is that these exosomal formulations are demonstrating results that
free STING agonists and systemic IL-12 were unable to achieve due
to significant limitations in safety and therapeutic index, opening
up the possibility that these two promising targets can benefit
cancer patients,” said David Mauro, M.D., Ph.D., Chief Medical
Officer of Codiak. “We are enthusiastic about moving these programs
into Phase 2 early next year while continuing to monitor patients
from ongoing studies and submitting data to upcoming medical
meetings.”
Conference Call and
WebcastCodiak will host a conference call and webcast
today at 8:00 a.m. ET. The webcast may be accessed through the
“News & Events” page in the “Investors & Media” section of
Codiak’s website at https://ir.codiakbio.com/news-events. A PDF of
the accompanying slides will be available for download. Phone
participants in the U.S and Canada may dial (800) 385-9715 and
refer to conference ID 3799112 (international callers please use
(409) 937-8965. To ensure timely access, participants are
encouraged to connect to the call 10 minutes before the start time
or to use the webcast link for listen-only access. The archived
webcast will be available on Codiak’s website beginning
approximately two hours after the event and will be available for
replay for at least 90 days after the event.
About exoSTING™ exoSTING is
Codiak’s exosome therapeutic candidate engineered to incorporate a
proprietary STING (Stimulator of Interferon Genes) agonist
inside the lumen of the exosome while expressing the exosomal
protein, PTGFRN, on the exosome surface to facilitate specific
uptake in tumor-resident antigen presenting cells. Codiak believes
that exoSTING has the potential to overcome certain limitations of
free STING agonists, and to enhance the therapeutic index and
selectivity of delivery to desired cells in the tumor
microenvironment.
About exoIL-12™ exoIL-12 is
Codiak’s exosome therapeutic candidate engineered to display fully
active IL-12 on the surface of the exosome, using the exosomal
protein, PTGFRN, as a scaffold, and designed to facilitate potent
local pharmacology at the injection site with precisely quantified
doses. By limiting systemic exposure of IL-12 and associated
toxicity, Codiak hopes to enhance the therapeutic index with
exoIL-12, delivering a more robust tumor response, dose control and
an improved safety profile. Codiak intends to focus development of
exoIL-12 on tumors that have, in previous clinical testing, shown
clinical responses to IL-12 used as a monotherapy.
About the engEx® PlatformCodiak’s
proprietary engEx Platform is designed to enable the development of
engineered exosome therapeutics for a wide spectrum of diseases
and to manufacture them reproducibly and at scale to
pharmaceutical standards. By leveraging the inherent biology,
function and tolerability profile of exosomes, Codiak is developing
engEx exosomes designed to carry and protect potent drug molecules,
provide selective delivery and elicit the desired pharmacology at
the desired tissue and cellular sites. Through its engEx Platform,
Codiak seeks to direct tropism and distribution by engineering
exosomes to carry on their surface-specific targeting drug
moieties, such as proteins, antibodies/fragments, and peptides,
individually or in combination. Codiak scientists have identified
two exosomal proteins that serve as surface and luminal scaffolds.
By engineering the exosome surface or lumen and optimizing the
route of administration, Codiak aims to deliver engEx
exosomes to the desired cell and tissue to more selectively
engage the drug target, potentially enhancing the therapeutic index
by improving potency and reducing toxicity.
About Codiak BioSciences Codiak is
a clinical-stage biopharmaceutical company pioneering the
development of exosome-based therapeutics, a new class of medicines
with the potential to transform the treatment of a wide spectrum of
diseases with high unmet medical need. By leveraging the biology of
exosomes as natural intercellular transfer mechanisms, Codiak has
developed its proprietary engEx Platform to expand upon the innate
properties of exosomes to design, engineer and manufacture novel
exosome therapeutic candidates. Codiak has utilized its engEx
Platform to generate a deep pipeline of engineered exosomes aimed
at treating a broad range of disease areas, spanning oncology,
neuro-oncology, infectious disease and rare disease. For more
information, please visit www.codiakbio.com.
Forward-Looking StatementsThis
press release contains “forward-looking statements” within the
meaning of the Private Securities Litigation Reform Act of 1995,
including, among other things, statements concerning the clinical
development and therapeutic potential of exoSTING and exoIL-12. Any
forward-looking statements in this press release are based on
management’s current expectations of future events and are subject
to a number of risks and uncertainties that could cause actual
results to differ materially and adversely from those set forth in
or implied by such forward-looking statements. For a discussion of
these risks and uncertainties, and other important factors, any of
which could cause our actual results to differ from those contained
in the forward-looking statements, see the section entitled “Risk
Factors” in Codiak’s Annual Report on Form 10-K for the
year ended December 31, 2021, and in subsequent filings with
the Securities and Exchange Commission, as well as discussions of
potential risks, uncertainties and other important factors in
Codiak’s subsequent filings with the Securities and Exchange
Commission. All information in this press release is current as of
the date of this report, and Codiak undertakes no duty to update
this information unless required by law.
1 Gokhale MS, Vainstein V, Tom J, et al. Single
low-dose rHuIL-12 safely triggers multilineage hematopoietic and
immune-mediated effects. Exp Hematol Oncol. 2014;3(1):11. Published
2014 Apr 11. doi:10.1186/2162-3619-3-11
Investor Contact:Christopher
TaylorVP, Investor Relations and Corporate Communications T:
617-949-4220E: investor@codiakbio.com
Media Contact:Cory TrombleeScient
PRmedia@codiakbio.com
Codiak BioSciences (NASDAQ:CDAK)
Historical Stock Chart
From Mar 2024 to Apr 2024
Codiak BioSciences (NASDAQ:CDAK)
Historical Stock Chart
From Apr 2023 to Apr 2024