Tessera Therapeutics Presents New Preclinical Data Highlighting Advancements Across Its Portfolio Programs and Platforms at the American Society of Gene and Cell Therapy 27th Annual Meeting
May 10 2024 - 6:00AM
Tessera Therapeutics, a biotechnology company pioneering a new
approach to genome engineering through the development of its Gene
Writing and delivery platforms, today presented progress across its
platforms and preclinical programs, including approximately 50%
correction of the most common mutation in AATD in vivo in mouse
disease models and first-time demonstration of efficient in vivo
rewriting of the HBB locus responsible for SCD in humanized mice.
Additional data were presented on in vivo correction of pathogenic
mutations responsible for phenylketonuria (PKU) and Wilson’s
Disease (WD), delivery advances to HSCs and T cells, and whole gene
writing to generate tumor-killing CAR-T cells, including
proof-of-principle of same-day manufacturing. These new data are
shared in four oral presentations and two poster presentations at
the American Society of Gene and Cell Therapy (ASGCT) Annual
Meeting taking place in Baltimore, Maryland, May 7 – 11, 2024.
“We have achieved substantial advances across our Gene Writing
and delivery platforms and are focused on driving our therapeutic
programs into the clinic,” said Michael Severino, M.D., CEO of
Tessera Therapeutics. “We are particularly excited about the highly
efficient correction to wild-type that we are seeing in preclinical
models for AATD, which exceeds levels seen in asymptomatic carriers
of the causative mutation, and the progress we are making on in
vivo HSC rewriting in SCD that we believe can enable true
correction to wild-type without complex stem cell mobilization and
ex vivo cell processing or toxic chemotherapy conditioning.”
Michael Holmes, Ph.D., CSO of Tessera Therapeutics added, “We
have demonstrated what we believe are industry leading correction
levels and the highest fidelity we are aware of across each of our
liver rewriting programs in PKU, AATD, and WD, which is a testament
to the exceptional team at Tessera and the power and capabilities
of our Gene Writing and delivery platforms.”
AATD
- AATD is a condition in which the
liver makes an abnormal form of the alpha-1 antitrypsin (AAT)
protein that causes both lung and liver disease
- In a humanized SERPINA1 mouse model
of AATD, Gene Writers achieved an average of 49% rewriting
efficiency in whole liver samples at a dose of 0.1 mg/kg, with a
fidelity ratio of intended to unintended edits at the target locus
of 198 to 1
- In a transgenic PiZ mouse model in
AATD, an average of 55% in vivo correction was observed at a dose
of 0.5 mg/kg in whole liver samples, which resulted in an average
of approximately 93% of mRNA transcripts being corrected
- This level of efficiency was
associated with a greater than 5-fold increase in serum
concentration of the wild-type AAT protein, and a decrease in
aggregates of misfolded mutant AAT protein in mouse livers on
histological examination
SCD
- Gene Writers achieved
therapeutically relevant levels of HBB rewriting in vivo in
humanized mice, with an average efficiency of 25-27% in LT-HSCs
after a single dose
- In a repeat dose study, average HBB
rewriting levels of 44% were observed upon administering a second
dose, suggesting the potential to re-dose and see further increases
in correction
- Additional data showed that HSCs
edited in vitro retained their normal function to support
hematopoiesis and development of multiple blood cell types upon a
secondary bone marrow transplant in mice
PKU
- In a compound heterozygous mouse
model containing one allele of the PAH R408W mutation, the most
common disease-causing mutation for severe PKU, Gene Writers
achieved an average of ~42% rewriting in whole liver samples, which
corresponds to an estimated 70% correction in hepatocytes1
- These rewriting efficiencies were
comparable to that achieved in a homozygous mouse model for the
R408W mutation and resulted in normalized levels of
phenylalanine
- These results support the potential
therapeutic application of Gene Writers for PKU patients that carry
at least one copy of the R408W mutation
WD
- Gene Writers achieved an average of
~60% of alleles corrected in vivo in whole liver samples, which
resulted in an average of ~89% of corrected mRNA transcripts in a
humanized Wilson’s Disease mouse model with the H1069Q mutation,
the most common mutation in North America and Europe
- This level of efficiency was
associated with restored copper physiology, with urine copper
excretion diverted to feces and significant reductions in hepatic
copper accumulation observed
- Correction levels of the H1069Q
mutation in this mouse model appeared stable for the duration of
the study (12 weeks), with corresponding reductions of hepatic
copper observed
Engineered CAR-T Cells
- Gene Writers can integrate CAR
transgenes into T cells at an average efficiency of 42% in vitro
resulting in the generation of functional CAR-T cells that show
tumor killing in vitro and in vivo
- Proof-of-principle studies in
developing a same-day manufacturing process showed the CAR-T cells
generated could clear tumor in vivo when administered to mice
- Additional details will be presented
by Kassi Stein, Ph.D., on Saturday, May 11th, 2024, from 11:45 a.m.
– 12:00 p.m. EDT
Delivery
- Novel LNPs were developed and shown
to efficiently deliver a reporter gene to extra-hepatic tissues in
vivo, including to an average of ~95% of LT-HSCs in mice and
non-human primates (NHPs), and an average of ~80% and ~40% of T
cells in mice and NHPs, respectively
- Gene Writers delivered as LNP-RNA
drove an average editing efficiency of 76% in LT-HSCs in vivo in
mice treated with a surrogate reagent targeting the beta-2
microglobulin locus
1Based on the assumption that 60% of liver cells are
comprised of hepatocytes
About Tessera Therapeutics
Tessera Therapeutics is pioneering a new approach to genome
engineering through the development of its Gene Writing™ and
delivery platforms, with the aim to unlock broad new therapeutic
frontiers. Our Gene Writing platform is designed to write
therapeutic messages into the genome by efficiently changing single
or multiple DNA base pairs, precisely correcting insertions and
deletions, or adding exon-length sequences and whole genes. Our
proprietary lipid nanoparticle delivery platform is designed to
enable the in vivo delivery of RNA to targeted cell types. We
believe our Gene Writing and delivery platforms will enable
transformative genetic medicines to not only cure diseases that
arise from errors in a single gene, but also modify inherited risk
factors for common diseases and create engineered cells to treat
cancer and potentially autoimmune and other diseases. Tessera
Therapeutics was founded in 2018 by Flagship Pioneering, a life
sciences innovation enterprise that conceives, creates, resources,
and develops first-in-category bioplatform companies to transform
human health and sustainability.
For more information about Tessera, please visit
www.tesseratherapeutics.com.
Contact
Kristin Politi, PhDLifeSci Communications,
LLCkpoliti@lifescicomms.com