SAN
DIEGO, April 30, 2024 /PRNewswire/ -- Denovo
Biopharma LLC (Denovo), a pioneer in applying precision medicine to
the development of innovative therapies, today announced that the
California Institute for Regenerative Medicine (CIRM) has awarded a
$11.8M grant for further development
of DB107, Denovo's DGM7™ biomarker–guided late–stage gene therapy,
for high–grade glioma (HGG) including glioblastoma (GBM), a
malignant brain cancer. CIRM has awarded the grant to
Dr. Noriyuki Kasahara, MD, PhD, at the University of California San Francisco (UCSF) and a
group of investigators at California universities to conduct a
Phase 1/2 clinical trial studying DB107 in patients with
newly–diagnosed HGG.
We are thrilled to continue the clinical
development of our biomarker-guided DB107 gene therapy in HGG
including GBM.
The trial, titled "A Phase I/IIa Study to Evaluate the Efficacy
of DB107–RRV, Administered to Subjects at Time of Resection and
Intravenously Thereafter, in Combination with DB107–FC and
Radiation Therapy or DB107–FC, Temozolomide (TMZ) and Radiation
Therapy in Patients with Newly–Diagnosed High–Grade Glioma," plans
to enroll up to 70 patients. The trial aims to demonstrate
improvements in progression–free survival.
DB107 consists of two components: DB107–RRV (vocimagene
amiretrorepvec) as a prodrug activator gene therapy and DB107–FC
(extended-release 5–fluorocytosine [5–FC]) as an oral prodrug.
DB107–RRV, a retroviral replicating vector (RRV) administered
intratumorally and intravenously, converts the orally administered
5–FC into the potent chemotherapy agent 5–fluorouracil (5–FU)
locally at the tumor sites. This enables intratumoral
concentrations 30–50 times of those achievable by 5–FU
systemic administration, killing tumor cells while minimizing the
systemic exposure and off–target toxicities of 5–FU. Using its
proprietary biomarker discovery platform including whole genome
sequencing (WGS) and artificial intelligence (AI), Denovo
discovered the novel germline genetic biomarker, Denovo Genomic
Marker 7 (DGM7), which is located in the SHROOM3 gene
intron. Retrospective analysis of an earlier randomized clinical
trial in patients with recurrent HGG suggested improved overall
survival in DGM7–positive patients treated with DB107.
"We are excited to conduct this novel trial which will be
investigating several new approaches for the first time in patients
with newly–diagnosed high–grade glioma. In addition to DB107–RRV
being administered both intratumorally and intravenously to provide
more exposure, this study will also use the RRV in conjunction with
radiation therapy and chemotherapy with temozolomide. In addition
to the direct therapeutic effect of gene therapy, glioma cells will
be sensitized to these standard therapies by 5–FU generated
directly within the patient's tumor from DB107–FC. We are also
excited to test the DGM7 biomarker to see if we can identify
patients who may benefit the most from this unique gene therapy
approach," said Dr. Kasahara.
DGM7 status will be determined at the time of enrollment to
prospectively assess the effect of the biomarker on clinical
outcomes. The study will be conducted at UCSF (Dr. Noriyuki Kasahara, MD, PhD, and Dr. Nicholas Butowski, MD), University of Southern California (USC) (Dr. Thomas
Chen, MD, PhD), and University of
California San Diego (UCSD) (Dr. David Piccioni, MD, PhD), and will be managed by
Anova Enterprises, Inc.
"We are thrilled to continue the clinical development of our
biomarker–guided DB107 gene therapy in patients with HGG including
GBM, a major unmet medical need with less than 5% of GBM patients
surviving 5 years," said Dr. Matthew
A. Spear, MD, Denovo's Chief Medical Officer and Chief
Development Officer. "Alongside our recent announcement of positive
results in a Phase 2b clinical trial of our DGM4
biomarker–guided DB104 drug (liafensine) in treatment–resistant
depression, the CIRM grant provides continued validation of
Denovo's approach to discovering new genetic biomarkers and
developing biomarker–guided therapies."
About HGG and GBM
The most common type of high–grade
glioma (HGG) is glioblastoma (GBM), which is also the most common
type of adult primary brain cancer, with 18,000 newly–diagnosed
patients in the US and 13,000 deaths annually. Standard treatments
for patients with newly–diagnosed GBM can include surgery followed
by radiation and chemotherapy, but treatment options are limited.
The 5–year survival rate of patients with GBM is less than 5%.
About DB107 and the DGM7™ Biomarker
DB107 is an
investigational combination product consisting of the DB107–RRV
(vocimagene amiretrorepvec) gene therapy and DB107–FC
(extended–release 5–fluorocytosine) oral prodrug. DB107–RRV, an
innovative proprietary retroviral replicating vector (RRV), is
combined with DB107–FC to selectively infect and kill cancer cells
while stimulating a robust and durable anti–cancer immune response
against a tumor with minimal toxicity. DB107 has been tested
clinically in solid tumors including recurrent high–grade glioma
(rHGG) and colorectal cancer, most recently in a randomized
403–patient Phase 2/3 trial in rHGG including glioblastoma
(GBM). Using its proprietary biomarker discovery platform, Denovo
discovered the novel genetic biomarker, DGM7, which has been shown
to be associated with treatment response to DB107 in patients with
rHGG including GBM. DB107 has received Fast Track Designation and
Breakthrough Therapy Designation from the FDA, as well as Orphan
Drug Designations from the FDA and EMA.
About Denovo Biopharma
Denovo Biopharma LLC (Denovo)
is a clinical–stage biopharmaceutical company that uses a novel
biomarker discovery platform including whole genome sequencing
(WGS) and artificial intelligence (AI) to find new genetic
biomarkers predictive of drug efficacy, and then uses these
biomarkers to execute efficient clinical trials in targeted patient
populations to increase the probability of success. Denovo has
eight late–stage drugs in its pipeline addressing major unmet
medical needs in oncology and central nervous system diseases; most
of the pipeline are first–in–class drugs with global rights. Denovo
recently announced a major breakthrough in treatment–resistant
depression (TRD) with its DGM4™ biomarker–guided DB104 drug
(liafensine, a potential first–in–class triple reuptake
inhibitor for TRD). The global Phase 2b clinical trial of
DB104 in DGM4–positive patients with TRD demonstrated strikingly
positive results, with highly significant improvements in symptoms
of depression seen in DGM4–positive patients. Visit
www.denovobiopharma.com for additional information.
Contact
Michael F.
Haller, Chief Business Officer
Denovo Biopharma LLC
mhaller@denovobiopharma.com
View original content to download
multimedia:https://www.prnewswire.com/news-releases/cirm-awards-11-8-million-grant-for-clinical-trial-in-high-grade-glioma-including-glioblastoma-using-db107--a-novel-dgm7-genetic-biomarker-guided-gene-therapy-302131547.html
SOURCE Denovo Biopharma LLC