Lilly Cardiometabolic New Drug Domestic Clinical, Qilu, Novartis, Sanofi... RNAi therapy involved in the country?

On September 15, according to the official website of CDE, the clinical trial application submitted by Eli Lilly Cardiometabolic New Drug LY3819469 Injection in China was accepted (acceptance number: JXHL2200285

From: CDE website

Dicerna and Eli Lilly have reached a collaboration on 2 RNAi therapies into the clinical phase

LY3819469 is a new drug under development for cardiometabolic that has been approved by the FDA in May 2021 and is currently conducting a Phase I clinical study of cardiometabolic diseases (registration number: NCT04914546).

LY3819469 is an RNAi drug

Under the terms of the agreement, Dicerna will receive an advance payment of $100 million and an equity investment

The collaboration is primarily based on Dicera's proprietary GalXC™ RNAi technology, a technology platform designed to drive the development of the next generation of RNAi-based therapies to silence disease-causing genes

Didrina's original RNAi technology platform was designed primarily for the field of liver disease, but Dcerna is currently exploring other areas, and its new application of RNAi technology and GalXC-Plus expands the function and application

LY3819469 is the second clinical product developed by the two companies in cooperation with the second clinical stage product, after in November 2020, another RNAi therapy candidate of the company, LY3561774, has been approved by the FDA for clinical trial, and is currently conducting a phase II clinical study of hyperlipidemia (registration number: NCT05256654), which has not been reported to the domestic clinic

LY3819469 Gantt chart of global development progress

From: Insight Database Web (http://db.

In addition to the two products, which are already in the clinical stage, the two companies are also working together to advance the development of multiple preclinical products, planning to collaborate on more than 10 targets

Dicerna has worked extensively with MNC on a $3.

Dicerna collaborative project

From: Corporate website

In 2017, Boehringer Ingelheim partnered with Didrina to develop a non-alcoholic steatohepatitis (NASH) drug

In 2018, Alexion partnered with Didrina to develop RNAi therapies

In 2019, Roche and Didrina announced a global licensing and research collaboration

The hepatitis B gene therapy RG6346 (RO7445482, DCR-HBVS), developed in collaboration with Dicerna and Roche, is currently conducting a joint RG6346 Phase II trial (registration number: NCT04225715)

RG6346 Gantt chart of global development progress

From: Insight Database Web

Previously, Dicerna disclosed data from a Phase I clinical trial of RG6346, which showed that RG6346 produced a substantial, persistent decrease in hepatitis B surface antigen in subjects after 4 months of treatment, and remained

In November 2019, Novo Nordisk and Dicerna, which have been deeply involved in metabolic diseases for many years, announced a global licensing and research collaboration
focusing on cardiometabolic diseases.
Since then, Novo Nordisk has worked closely with Diarna and has explored more than 30 hepatocyte targets involving indications for non-alcoholic steatohepatitis, type 2 diabetes, obesity and more
.

But Novo Nordisk did not stop there, acquiring Dicerna in December 2021 for a US$3.
3 billion investment to further accelerate RNAi drug discovery and expand the use of RNAi technology, becoming one of the highest-premium acquisitions in the pharmaceutical sector that
year.

Nordisk acquires Dicerna

From: Insight Database Web

Novo Nordisk previously expected to launch clinical development
of the first target this year.
According to incomplete statistics, so far in 2022, in addition to the domestic declaration of LY3819469, from a global perspective, there are two other products cooperated with Eli Lilly, LY3849891 and LY3561774 research and development progress to a new stage
.

LY3849891, LY3561774 The R&D progress in 2022 has been advanced to a new stage

From: Insight Database Web

LY3849891 was first announced overseas in May this year, and is currently conducting a Phase I clinical trial of non-alcoholic fatty liver disease in Japan and the United States (registration number: NCT05395481).

LY3561774 launched a Phase II clinical study
in February this year.

In addition, it is worth mentioning that Alnylam, who has been fighting with Dicerna patent litigation for many years, reached a cooperation with Diarna in April 2020 to develop a drug for the treatment of
liver disease associated with α-1 antitrypsin (A1AT) deficiency (α-1 liver disease) on ALN-AAT02 and DCR-A1AT 。 In addition, the two companies have agreed to cross-license their respective intellectual property rights for their research programs in Lumasiran and Nedosiran, which treat PH
.

It is believed that the joint efforts of the two RNAi therapy giants will bring more blockbuster products
to the RNAi track in the future.

228 RNAi therapies worldwide in Roche, Novartis, Sanofi.
.
.
Involved in the country

RNAi is not an emerging technology, but due to its stability, in vivo delivery technology and other reasons, RNAi drug development once fell into a trough, until 2018, the Alnylam RNAi drug ONPATTRO (PATISIRAN) was approved by the FDA for marketing, once again making the RNAi track the focus
.
Since then, the RNAi space has been actively
traded.

In 2019, Novartis spent $9.
7 billion to acquire The Medicines Company for Lnclisiran, a cholesterol-lowering RNAi drug;

In 2020, Blackstone and Alnylam reached a $2 billion funding partnership for R&D in the RNAi industry;

In 2021, in addition to Novo Nordisk's acquisition of Dicerna, GlaxoSmithKline's collaboration with Arrowhead has also attracted much attention, with GlaxoSmithKline introducing RNAi therapies for NASH for a total of more than $1 billion; .
.
.
.
.
.

At present, according to the Insight database, there are 228 RNAi therapies in the world, 99 of which have entered the clinical stage, of which 5 have been approved for listing, as follows:

5 RNAi therapies approved worldwide

From: Insight Database Web

For domestic enterprises, it is still in its infancy, with a total of 11 new drugs entering the clinical stage (including declared clinical), of which the fastest growing imported products, including Novartis Inclisiran and Sanofi Fitusiran, have been in the phase III clinical stage; Roche, Johnson & Johnson, Amgen and so on have layouts
.

In addition, the Kotrani introduced by Guangzhou Xiangxue Pharmaceutical has been approved for clinical practice in China in 2017, and the AB-729 introduced by Qilu is still in the clinical stage of
declaration.

From the perspective of the layout of domestic enterprises, the field is currently relatively blank, only SR043 and RBD106 of Ruibo Bio and HT101 3 domestic siRNA products of Suzhou Xingyao Kunze Bio have entered the clinical stage (including declared clinical).

11 domestic RNAi therapies have entered the clinical stage

From: Insight Database Web