Pathos Expands Pipeline With Worldwide License of Phase 2-ready Brain-penetrant, PRMT5 Inhibitor
15 Agosto 2024 - 7:00AM
Pathos AI, Inc. (www.pathos.com), a biotechnology company focused
on revolutionizing precision medicine in cancer by harnessing the
power of machine learning to transform drug development, announced
today the world-wide license of PRT811, a potent, selective, and
orally bioavailable brain penetrant SAM-competitive PRMT5 inhibitor
from Prelude Therapeutics.
PRT811 (renamed P-500) was developed by Prelude Therapeutics and
completed a Phase 1 trial in March 2023. The trial enrolled
patients with solid tumors including high-grade glioma and uveal
melanoma and has potential application in other indications with
high unmet need. Out of 16 patients with high-grade glioma with
isocitrate dehydrogenase mutations (IDH+) in the Phase 1 trial, two
confirmed complete responses (CR) were observed. At last follow-up,
1 response is ongoing and has lasted 31.0 months while the duration
of response for the second CR patient was 7.5 months. Additionally,
1 patient achieved an unconfirmed partial response (PR).
In addition, out of 23 uveal melanoma patients (10 patients with
splicing factor 3B subunit 1 (SF3B1) splicing mutations and 13
without an SF3B1 mutation), one confirmed PR (duration of response
of 10 months) and a second unconfirmed PR were observed, both in
patients SF3B1 mutations.
In the entire safety population (N=86), the most common adverse
events of any grade, with an incidence of >20% were nausea
(60.5%), vomiting (46.5%) fatigue (36.0%), constipation (29.1%),
and thrombocytopenia (24.4%), and were predominantly grade 1-2. The
most common adverse events (grade ≥3), occurring >5% were
thrombocytopenia (9.3%), anemia (9.3%), and fatigue (5.8%).
“These results from Prelude’s Phase 1 study are promising news
for high-grade glioma patients and clinicians, who still have
limited treatment options with chemotherapy and radiation that
hasn’t changed in decades. With our AI Platform, we aim to increase
the already encouraging response rate of P-500 through a novel
biomarker-driven strategy, ultimately bringing this medicine to
patients as efficiently as possible,” said Ryan Fukushima, Pathos
CEO.
“Prelude’s discovery engine has delivered a number of first- or
best-in-class precision medicines including PRT811, a molecule that
has shown early promise in the treatment of high-grade glioma. We
are confident that Pathos AI, sharing our passion for precision
medicine and commitment to serving cancer patients with high unmet
need, is an ideal company to drive the development of this molecule
forward for patients.” said Sean Brusky, Prelude CBO. "The
resources from this transaction will support advancing Prelude's
pipeline."
About P-500P-500 (previously PRT811) is a
selective, brain-penetrant small molecule inhibitor of protein
arginine methyltransferase 5 (PRMT5) that has the potential to
provide clinical benefit for patients with advanced solid tumors,
including high-grade glioma and uveal melanoma.
PRMT5 is an enzyme that adds methyl groups to proteins in cells
using a molecule called S-adenosylmethionine (SAM) which
regulates protein function and interactions. Several processes that
support cancer cell growth and spread depend on PRMT5, making P-500
relevant not only to advanced high-grade glioma and uveal melanoma
(in which objective responses to P-500 were observed in the Phase 1
clinical trial) but also to a number of other cancer indications.
Preclinical studies have demonstrated PRMT5 inhibition can
sensitize cancer cells to other treatments, expanding the
application of P-500 to combination therapy in additional
indications.
About PathosPathos is a clinical-stage
biotechnology company focused on re-engineering drug development,
leveraging the power of AI technologies to bring precision
medicines to market through partnership with biopharmaceutical
companies. Pathos has raised $40 million to accelerate the
development of precision medicines and to expand its platform,
combining computational approaches across multimodal real-world
data and patient-derived biological models. Additional information
can be found at www.pathos.com.
ContactsBusiness Development:
bd@pathos.comPress Inquiries: press@pathos.com