2/GPH101 (nula-cel) is a #CRISPR#Cas9#GeneEditing autologous #stem#cell-based #therapy in clinical development aimed to treat #SickleCellDisease. GPH101 is designed to directly correct the underlying mutation, thereby decreasing HbS production & restoring HbA expression #ASH22
3 $GRPH gene correction platform involves editing hematopoietic #stem cells found in the #bonemarrow that develop into various types of #blood#cells. Since red blood cells lose their genomic DNA during maturation-tracking #GeneEditing in mature cells via sequencing is impossible
4/The problem of the inability to mesure the efficacy of #GeneEditing in #SCD patients was solved by using immature red blood cells called #reticulocytes which retain their RNA and can be sequenced in order to assess the #gene correction levels after using nula-cel. #ASH22
5/Based on this knowledge, $GRPH sought to develop a single-cell RNA sequencing method that could measure #GeneEditing outcomes in reticulocytes. It first measured the genetic makeup of reticulocytes from healthy donors-AA, people with SCD trait-AS, & with #sicklecelldisease-SS.
6/Results from both experiments demonstrated the single-cell RNA sequencing method’s ability to precisely and reproducibly measure and differentiate the healthy donors - AA, people with SCD trait - AS and #SickleCellDisease patients - SS. #ASH22
1/WOW! hC Bioscience announces its first ever tRNA-based program for Duchenne muscular dystrophy (DMD). hC is developing anticodon engineered tRNAs as a potential treatment for DMD patients with shortened & nonfunctional dystrophin due to premature termination codons (PTCs). $XBI
2/Duchenne is a severe progressive disease which rapidly worsening children’s muscle function often using a wheelchair by early adolescence & eventually needing artificial ventilation to breathe. DMD is caused by mutations to dystrophin that affect about 300,000 males worldwide & PTCs account for approximately 26% of cases.
3/A nonsense mutation or premature termination codons (PTCs) is an alteration in the genetic code that prematurely halts the synthesis of an essential protein. The resulting disorder is determined by which protein cannot be expressed in its entirety and is no longer functional, such as dystrophin in Duchenne
1/As promised and after reading $CRBU latest Q1 2024 financial report here is my impression regarding @CaribouBio latest corporate status. As always - I have focused only on the main issues that I found to be the most interesting & relevant. Here’s my summary 🧵👇 $XBI #BioTech
2/IMO the most significant corporate event was $CRBU decision - due to internal portfolio prioritisation - to terminate the development of its CB-020 program - a preclinical allogeneic anti-POR1 CAR-NK cell therapy - a decision which narrowed dramatically the company’s pipeline.
3/Another major event was $CRBU announcement that it had received FDA clearance of its Investigational New Drug - IND application to evaluate CB-010 ability to treat patients with lupus nephritis (LN) & extrarenal lupus (ERL) Thus expending CB-010’s therapeutic potential. $XBI
1/@LineageCell presented promising data at the @FightBlindness Gene Therapy innovation summit - as part of #ARVO2024, from its clinical study of RG6501 (OpRegen) - a retinal pigment epithelial Cell therapy aimed to treat age-related macular degeneration dry AMD. $LCTX $RHHBY $XBI
2/@LineageCell has developed a unique technology that enables it to transplant specific cell types from a single pluripotent cell line thus creating “off the shelf” cell transplants platform for multiple conditions. $LCTX most advanced program is its OpRegen ocular platform. $XBI
3/Dry AMD leads to the loss of retina cells thus creating an area of geographic atrophy-GA, which leads to impaired vision & blindness. By using a subretinal injection of RPE cells into the eye OpRegen will be able to preserve or improve a patient’s vision
1/@WaveLifeSci today announced the approval of its first clinical trial application (CTA) for its RestorAATion-2 clinical trial of $WVE-006, Wave’s first-in-class RNA editing oligonucleotide, which is being developed for the treatment of alpha-1 antitrypsin deficiency-AATD. $XBI
2/WVE-006 is a first-in-class, GalNAc-conjugated RNA editing oligonucleotide aimed to correct the single base mutation in messenger RNA (mRNA) coded by the SERPINA1 Z allele, thereby enabling restoration and circulation of functional, wild-type alpha-1 antitrypsin (M-AAT) protein
3/RestorAATion-2 is a Phase 1b/2a open label study designed to evaluate the safety & tolerability of WVE-006 in individuals with AATD who have the homozygous Pi*ZZ mutation. $WVE remains on track to deliver proof-of-mechanism data - restoration of M-AAT protein in serum, in 2024.
1/@VerveTx announced that due to observed laboratory abnormalities associated with $VERV-101, it has decided to pause enrollment in its Heart-1 clinical trial. Verve is conducting an investigation & will work with regulatory authorities to define a path forward for VERVE-101 $XBI
2/VERVE-101 is being evaluated in the Heart-1 Phase 1b clinical trial with trial endpoints of safety and tolerability as well as changes in blood PCSK9 protein and low-density lipoprotein cholesterol (LDL-C) levels in patients living with heterozygous familial hypercholesterolemia (HeFH), established atherosclerotic cardiovascular disease (ASCVD), and uncontrolled hypercholesterolemia
3/6 participants have been dosed at 0.45 mg/kg of VERVE-101 from a total of 13 participants. For the first 5 in the 0.45 mg/kg cohort (with follow-up of >28 days) $VERV-101 demonstrated time-averaged LDL-C reductions ranging from 21% to 73%, & averaging 46% (cut-off date 3/18/24)
1/@CaribouBio announced that preclinical data from its CB-012 program - an allogeneic anti-CLL-1 CAR-T cell therapy aimed to treat relapsed or refractory acute myeloid leukemia (r/r AML), will be presented at the upcoming #AACR24 held April 5-10, 2024 in San Diego. $CRBU #CRISPR
2/CB-012 is an anti-CLL-1 CAR-T cell therapy engineered with five genome edits, enabled by @CaribouBio’s patented next-generation CRISPR technology platform, which uses Cas12a chRDNA Gene Editing platform to significantly improve the specificity of genome edits. $CRBU
@CaribouBio 3/CB-012 is the first allogeneic CAR-T cell therapy with both checkpoint disruption, through a PD-1 knockout, and immune cloaking, through a B2M knockout and B2M–HLA-E fusion protein insertion; both armoring strategies are designed to improve antitumor activity.