Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a
clinical stage biopharmaceutical company focused on developing
multimodal biological immunotherapies to help patients fight
cancer, today announced updated interim survival data from the
ongoing randomized phase 2 clinical trial of CAN-2409 plus
valacyclovir (prodrug), together with standard of care (SoC)
chemoradiation, followed by resection for borderline resectable
pancreatic ductal adenocarcinoma (PDAC). Survival data were updated
with eight months of further follow-up since the first analysis
presented at the 2023 Society for Immunotherapy (SITC) Annual
Meeting. Based on the data presented at SITC, the U.S. Food and
Drug Administration (FDA) granted Fast Track Designation to the
Company for CAN-2409 in combination with valacyclovir for the
treatment of patients with PDAC in December 2023.
“Given frequent recurrence and short survival
with SoC chemotherapy for non-metastatic PDAC, effective new
treatment options are urgently needed,” said Garrett Nichols, MD,
MS, Chief Medical Officer of Candel. “We are very encouraged by the
improved survival associated with CAN-2409, which has been shown to
be durable after prolonged follow-up based on the updated data
shown in this randomized clinical trial. CAN-2409 was generally
well tolerated without significant additional local or systemic
toxicity when added to SoC chemoradiation.”
Data Highlights as of a March 29, 2024
Data Cut-off, Include:
- Prolonged and sustained survival
was observed after experimental treatment with CAN-2409 in patients
with borderline resectable PDAC (n=13)
- Estimated median overall survival
was 28.8 months in the CAN-2409 group versus only 12.5 months in
the control group.
- At 24 months, a survival rate of
71.4% was observed in CAN-2409 treated patients, after SoC
chemoradiation and prior to surgery, versus only 16.7% in the
control group. At 36 months, a survival rate of 47.6% was estimated
in patients who received CAN-2409, together with SoC chemoradiation
prior to surgery, versus only 16.7% in the control group.
- Importantly, 4 out of 7 patients
who received CAN-2409 were still alive at the time of data cut-off,
with 2 patients surviving more than 50.0 months from enrollment.
Only 1 out of 6 patients, randomized to control SoC chemotherapy,
remained alive at data cut-off (alive at 50.6 months).
- Previous analysis of blood and
resected tumors showed consistent and robust activation of the
immune response after experimental treatment with CAN-2409
- In pancreatic tissue of patients
treated with CAN-2409 plus prodrug together with SoC (but not SoC
alone), dense aggregates of CD8+ granzyme B positive cytotoxic
tumor infiltrating lymphocytes, dendritic cells, and B cells were
observed in the tumor microenvironment.
- Increased levels of soluble
granzymes B and H, as well as pro-inflammatory cytokines, including
IFN-γ, were observed in peripheral blood after CAN-2409
administration, but not after SoC.
- CAN-2409 continued to be associated
with a favorable safety/tolerability profile
- Addition of CAN-2409 regimen to SoC was generally well
tolerated, with no dose-limiting toxicities, including no cases of
pancreatitis
“The failure of conventional immunotherapy to
improve outcomes in pancreatic cancer is attributed to the highly
immunosuppressive tumor microenvironment, which is largely devoid
of immune cells,” said Paul Peter Tak, MD, PhD, FMedSci, President
and Chief Executive Officer of Candel. “The immunological changes
induced by CAN-2409, evident in the pancreatic tissue and the
peripheral blood after administration, suggest that CAN-2409 is
able to change the balance between the tumor and the patient’s
anti-tumor immune response, which can convert progressive cancer
into a chronic disease associated with improved survival.”
About Candel Therapeutics
Candel is a clinical stage biopharmaceutical
company focused on developing off-the-shelf multimodal biological
immunotherapies that elicit an individualized, systemic anti-tumor
immune response to help patients fight cancer. Candel has
established two clinical stage multimodal biological immunotherapy
platforms based on novel, genetically modified adenovirus and
herpes simplex virus (HSV) gene constructs, respectively. CAN-2409
is the lead product candidate from the adenovirus platform and is
currently in ongoing clinical trials in non-small cell lung cancer
(NSCLC) (phase 2), borderline resectable PDAC (phase 2), and
localized, non-metastatic prostate cancer (phase 2 and phase 3).
CAN-3110 is the lead product candidate from the HSV platform and is
currently in an ongoing investigator-sponsored phase 1 clinical
trial in recurrent high-grade glioma (rHGG). Finally, Candel’s
enLIGHTEN™ Discovery Platform is a systematic, iterative HSV-based
discovery platform leveraging human biology and advanced analytics
to create new viral immunotherapies for solid tumors.
For more information about Candel,
visit: www.candeltx.com
About the Phase 2 Clinical Trial of
CAN-2409 in Non-Metastatic Pancreatic Cancer
This randomized, open-label phase 2 clinical
trial is designed to evaluate the safety, preliminary efficacy, and
biologic activity of a 2-3 injection regimen of CAN-2409 plus
prodrug (valacyclovir or acyclovir) in patients with borderline
resectable PDAC who are being treated with neoadjuvant
chemoradiation prior to resection. After a protocol amendment in
2022, when enrollment of patients with locally advanced PDAC was
discontinued, the clinical trial was designed to exclusively
focused on borderline resectable disease. The clinical trial
remains active but is not currently unrolling new patients. In a
previously completed phase 1b clinical trial, a highly significant
increase in the number of CD8+ tumor infiltration lymphocytes was
demonstrated at the site of the tumor after CAN-2409 treatment.
About CAN-2409
CAN-2409, Candel’s most advanced multimodal
biological immunotherapy candidate, is an investigational
off-the-shelf replication-defective adenovirus designed to deliver
the herpes simplex virus thymidine kinase (HSV-tk) gene to a
patient’s specific tumor and induce an individualized, systemic
immune response against the disease. HSV-tk is an enzyme that
locally converts orally administered valacyclovir into a toxic
metabolite that kills nearby cancer cells. Together this regimen is
designed to induce an individualized and specific CD8+ T cell
mediated response against the injected tumor and uninjected distant
metastases for broad anti-tumor activity, based on in situ
vaccination against a variety of tumor antigens. Because of its
versatility, CAN-2409 has the potential to treat a broad range of
solid tumors. Encouraging monotherapy activity as well as
combination activity with standard of care radiotherapy, surgery,
chemotherapy, and immune checkpoint inhibitors have previously been
shown in several preclinical and clinical settings. Furthermore, to
date, more than 1,000 patients have been dosed with CAN-2409 with a
favorable tolerability profile to date, supporting the potential
for combination with other therapeutic strategies without
inordinate concern of overlapping adverse events.
Currently, Candel is evaluating the effects of
treatment with CAN-2409 in NSCLC, borderline resectable PDAC, and
localized, non-metastatic prostate cancer in ongoing clinical
trials. CAN-2409, plus prodrug (valacyclovir), has been granted
Fast Track Designation by the FDA for treatment of PDAC or stage
III/IV NSCLC in patients who are resistant to first line PD-(L)1
inhibitor therapy and who do not have activating molecular driver
mutations or have progressed on directed molecular therapy. The
Company’s pivotal phase 3 clinical trial in prostate cancer is
being conducted under a Special Protocol Assessment by FDA.
About Pancreatic Ductal Adenocarcinoma
(PDAC)
Pancreatic cancer is a highly lethal malignancy,
and is the fourth leading cause of cancer-related death in the
United States among both men and women. Based on the National
Cancer Institute, Surveillance, Epidemiology and End Results (SEER)
database, pancreatic cancer is expected to account for 3.3% of all
new cancer cases with an estimated 64,050 new cases and estimated
50,550 deaths in 2023. Effective therapeutics for pancreatic
cancer, including PDAC, which accounts for 90% of all pancreatic
carcinomas, are urgently needed.
Surgical resection offers the only chance of
cure, thus a major therapeutic goal for subjects with
non-metastatic disease is to achieve complete tumor resection.
Surgical treatment (pancreaticoduodenectomy, also known as the
Whipple procedure) or total or distal pancreatectomy (depending on
tumor location) is generally the recommended treatment for patients
diagnosed with resectable cancer; the addition of adjuvant
chemotherapy has been shown to only slightly improve survival rates
(20 to 23 months). To this end, there has been increasing use
of neoadjuvant chemotherapy and chemoradiation regimens for
subjects with borderline resectable pancreatic ductal
adenocarcinoma. Neoadjuvant regimens are intended to debulk the
tumor, thereby increasing the proportion of patients who may become
eligible for surgical resection and achieve complete resection
(i.e., resection with negative margins, designated ‘R0 resection’).
Unfortunately, even when an R0 resection is initially achieved,
cures remain elusive as most patients experience disease recurrence
due to residual micrometastatic disease. In a recent meta-analysis
of 20 studies representing 283 patients with borderline resectable
PDAC, neoadjuvant FOLFIRINOX with or without radiotherapy, median
overall survival was only 22.2 months (95% CI, 18.8 to 25.6
months).
Immunotherapy with PD-1 antibodies with or
without CTLA-4 antibodies has been uniformly unsuccessful in
patients with PDAC due to the dense stroma that surrounds PDAC
tissue and the absence of tumor infiltrating lymphocytes.
Forward-Looking Statements
This press release includes certain disclosures
that contain “forward-looking statements,” within the meaning of
the Private Securities Litigation Reform Act of 1995, as amended,
including, without limitation, express or implied statements
regarding the timing and advancement of development programs,
including the timing and availability of additional data, key data
readout milestones, and expectations regarding the therapeutic
benefit of the Company’s programs, including the potential for its
programs to extend patient survival. The words “may,” “will,”
“could,” “would,” “should,” “expect,” “plan,” “anticipate,”
“intend,” “believe,” “estimate,” “predict,” “project,” “potential,”
“continue,” “target” and similar expressions are intended to
identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Any
forward-looking statements in this press release are based on
management’s current expectations and beliefs and are subject to a
number of risks, uncertainties and important factors that may cause
actual events or results to differ materially from those expressed
or implied by any forward-looking statements contained in this
press release, including, without limitation, those risks and
uncertainties related to the timing and advancement of development
programs; the Company’s ability to continue as a going concern;
expectations regarding the therapeutics benefit of the Company’s
programs; that final data from the Company’s pre-clinical studies
and completed clinical trials may differ materially from reported
interim data from ongoing studies and trials; the Company’s ability
to efficiently discover and develop product candidates; the
Company’s ability to obtain and maintain regulatory approval of
product candidates; the Company’s ability to maintain its
intellectual property; the implementation of the Company’s business
model, including strategic plans for the Company’s business and
product candidates, and other risks identified in the Company’s
filings, with the U.S. Securities and Exchange Commission (SEC)
including the Company’s most recent Annual Report on Form 10-K
filed with the SEC, and subsequent filings with the SEC. The
Company cautions you not to place undue reliance on any
forward-looking statements, which speak only as of the date they
are made. The Company disclaims any obligation to publicly update
or revise any such statements to reflect any change in expectations
or in events, conditions, or circumstances on which any such
statements may be based, or that may affect the likelihood that
actual results will differ from those set forth in the
forward-looking statements. Any forward-looking statements
contained in this press release represent the Company’s views only
as of the date hereof and should not be relied upon as representing
its views as of any subsequent date.
Investor ContactTheodore
Jenkins VP Investor Relations and Business Development Candel
Therapeutics, Inc.Tjenkins@candeltx.com
Media ContactAljanae ReynoldsDirectorWheelhouse
Life Science Advisorsareynolds@wheelhouselsa.com
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