One injection is effective for a long time, and the clinical data of the Nobel Prize team's second in vivo CRISPR therapy was released

On November 12, 2022, Intellia Therapeutics announced positive interim data from its second in vivo CRISPR gene-editing therapy, NTLA-2002
, in a Phase 1/2 clinical trial for the treatment of hereditary angioedema (HAE).
。 These clinical data were obtained from 10 adult patients with hereditary angioedema (HAE) at different doses treated with NTLA-2002, and the results showed significant reductions in pathogenic kallikrein in all patients treated with different doses (25 mg, 50 mg, 75 mg), 64%, 81%, and 92%
at weeks 32, 22, and 16, respectively 。 In addition, the clinical trial also showed a significant decrease in the frequency of hereditary angioedema (HAE) attacks in patients after receiving a single treatment, with an average decrease of 91% and 78% in the 25 mg and 75 mg dose groups from week 1 to week 16 after treatment (the 50 mg dose group has not yet reached the observation time at week 16).

The first three treated patients have been 5.
5-10.
6 months without relapse
to date.
NTLA-2002 was generally well tolerated in all dose groups, with most adverse events being mild
.

Intellia said the clinical data showed a treatment, sustained response to NTLA-2002 and confirmed the power
of the company's CRISPR-based gene-editing platform.

Intellia Therapeutics is a gene-editing therapy company
founded by Jennifer Doudna, the founder of CRISPR gene editing technology and Nobel laureate 。 NTLA-2001 On June 26, 2021, Intellia Therapeutics published the results of the first clinical trial of in vivo CRISPR gene editing therapy in the international top medical journal "New England Journal of Medicine" (NEJM), which greatly expanded the application scope of CRISPR gene editing therapy, and directly injected CRISPR components can carry out efficient gene editing in vivo, opening up new ways for the treatment of many genetic diseases.
opened a new era of medicine"
.
The therapy, called NTLA-2001, delivers sgRNAs carrying sgRNAs targeting the disease-causing gene TTR gene and the mRNA sequence of the optimized spCas9 protein to the liver
via lipid nanoparticle (LNP) vectors.
It is used for the treatment of transthyretin amyloidosis (ATTR).

AATR is a serious, life-threatening, rare genetic disorder estimated to affect approximately 50,000 people worldwide, characterized by the accumulation
of misfolded transthyretin (TTR) proteins in tissues such as nerves and the heart.
On June 24, 2022, Intellia announced interim data from the latest Phase 1 clinical trial of NTLA-2001 therapy, which was positive, and the decline in TTR protein levels in the serum after a single dose was stable and sustained
for up to 12 months 。 The main results were as follows: 1.
The decrease in TTR protein levels in the serum of patients was maintained in all four groups with different doses, the follow-up time of the low-dose group (0.
1mg/kg and 0.
3mg/kg group) reached 12 months, and the follow-up period of the high-dose group (0.
7mg/kg and 1.
0mg/kg group) reached 6 months
.
2.
In the 1.
0mg/kg dose group, the serum TTR protein level was reduced by 93% on average and 98% on the 28th day after administration, and the effect was maintained
in 6-9 months of follow-up 。 This report is based on extended follow-up data for 15 patients with hereditary transthyretin amyloidosis with multiple neuropathy (ATTRv-PN) who were divided into four dose groups in the first part of the trial: 0.
1 mg/kg (3 people), 0.
3 mg/kg group (3 people), 0.
7 mg/kg group (3 people), and 01.
0 mg/kg group (6 people).

In the highest dose group (1.
0 mg/kg), 6 treated patients had a 93% reduction in mean serum TTR protein levels at day 28 and a maximum reduction of 98%.

This reduction was maintained at 6 to 9 months of follow-up (6 months for 3 people and 9 months follow-up for 3 people), with an average reduction of 93%.

In the 0.
7 mg/kg dose group, the 86% mean serum TTR protein reduction observed at day 28 was also maintained
at 6 months of follow-up.
In addition, in the 0.
1 mg/kg and 0.
3 mg/kg groups, the follow-up time reached 12 months, and the reduction in serum TTR protein was also maintained
.
Notably, patients in the 0.
3 mg/kg group had an 89%
reduction in mean serum TTR at 12 months.
John Leonard, president and CEO of Intellia, said these interim data show more clearly the therapeutic potential
of NTLA-2001 therapy for patients with ATTR amyloidosis.
These data further underscore the power of genomic drugs and raise the likelihood of success for Intellia's broader in vivo genome editing platform, and also look forward to advancing the clinical development
of the first in vivo CRISPR therapy administered systemically and in vivo.
NTLA-2002 On November 12, 2022, Intellia announced the latest clinical progress
of its second in vivo CRISPR gene-editing therapy, NTLA-2002.
Hereditary angioedema (HAE) is a rare genetic disorder that affects 1 in 50,000 people
.
It is characterized by severe, recurrent, and unpredictable episodes of inflammation in various organs and tissues of the body, making patients feel painful, debilitating, and even life-threatening
.
Current treatment options are usually lifelong and require chronic intravenous or subcutaneous administration twice weekly, or daily oral administration
.
However, even with long-term medication, breakthrough attacks
can still occur.
Kallikrein inhibition is a clinically proven strategy
to prevent hereditary angioedema (HAE).
The therapeutic principle of NTLA-2002 is to deliver the KLKB1 gene targeted to liver cells through LNP CRISPR gene editing, thereby inhibiting the production of kallikrein, which in turn inhibits the production of bradykinin, and the overproduction of bradykinin can lead to the onset
of hereditary angioedema (HAE).

The data published are based on the results of 10 patients at different doses (3 in the 25 mg group, 4 in the 50 mg group, and 3 in the 75 mg group
) in this phase 1/2 clinical trial.

Results showed that significant decreases in kallikrein were observed in patients in all three dose groups, with a 64% decrease in the 25 mg group at week 32, an 81% decrease in the 50 mg group at day 22 post-treatment, and a 92%
decrease in the 75 mg dose group at week 16 after treatment.

In addition to plasma kallikrein levels, the study looked at the rate of hereditary angioedema (HAE) episodes in patients and showed that the 25 mg and 75 mg dose groups experienced an average decrease of 91% and 78% in the 1st to 16th weeks after treatment
.
The first three treated patients have been 5.
5-10.
6 months without relapse
to date.
In addition, NTLA-2002 was generally well tolerated in all dose groups, with most adverse events being mild
.
The most common adverse event was an infusion-related reaction, mostly grade 1, which resolved within a day
.
To date, no dose-limiting toxicities, serious adverse events, and grade 3 and above adverse events have been observed, and no clinically significant abnormalities have been observed
.
Dr.
John Leonard, CEO of Intellia, said the preliminary data from this clinical trial is an important milestone
for Intellia and people around the world who suffer from genetic disorders such as hereditary angioedema (HAE).
This supports the potential of a single dose of NTLA-2002 to permanently prevent the onset
of hereditary angioedema (HAE).
These results also reaffirm the power of Intellia's genome editing methods and modular platforms
.
This is the second clinical data for in vivo CRISPR gene-editing therapy in history, and once again shows that target cells in the human body can be precisely edited to treat genetic diseases
with a single, systemic administration of CRISPR-based therapies.