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The field of the central nervous system has returned to the vision
of big pharmaceutical companies such as Pfizer and Roche with the help of new technologies such as gene therapy and nucleic acid therapy.
Alzheimer's disease and neurodegenerative diseases continue to receive the most attention
.
of big pharmaceutical companies such as Pfizer and Roche with the help of new technologies such as gene therapy and nucleic acid therapy.
Alzheimer's disease and neurodegenerative diseases continue to receive the most attention
.
Pfizer's $11.
6 billion acquisition of Biohaven, made public in May, remains the largest acquisition
of the year.
For Pfizer, this is a move to rearrange the central nervous system (CNS); From an industry perspective, the return of multinational pharmaceutical companies is an important symbol
of the recovery of drug development in this field.
And all kinds of transactions are the main way to
return.
According to R&D statistics, so far in 2020, there have been 15 transactions of more than US$500 million in the CNS field by multinational pharmaceutical companies, including cooperative development, project introduction and corporate acquisition
.
And their return to the "posture" shows that Alzheimer's disease (AD) is still the most concerned, and new targets and new technologies are gradually becoming the focus of
research and development.
Defeat AD, fight AD
Defeat AD, fight ADSeven deals were explicitly related to
AD or neurodegenerative diseases.
This is still the main direction of
industry investment.
A few years ago, some multinational pharmaceutical companies announced their withdrawal from the CNS field, and some reduced their investment
in this field.
One of the root causes is the failure
of AD drug development.
Some of the pharmaceutical companies that lost AD chose "where to fall and where to get up"
.
In 2017, Merck failed the phase III clinical trial of the AD drug verubecestat under development, after which the company gradually withdrew from the AD competition
.
In August, it entered into a $1.
1 billion partnership with Cerevance to leverage Cerevance's NETSseq
Technology platforms screen new targets and return to this field
.
GlaxoSmithKline (GSK) closed its China R&D center
in 2017.
The R&D center focuses on AD, Parkinson's and various pain diseases
.
In 2021, GSK partnered with Alector to develop two antibodies, AL001 and AL101
, for neurodegenerative diseases.
Roche's AD drug gantenerumab has also experienced two clinical study failures, but the drug is still in its pipeline, and it was also designated as a breakthrough therapy by the FDA in 2021
.
Roche was the first to lay out in this field, and the two cooperation in 2020 and 2021 are still in this difficult field
.
In June 2022, the company suffered some setbacks when another amyloid product, crenezumab, declared a phase II clinical failure
.
The deals between Bristol-Myers Squibb (BMS) and AbbVie are also related to neurodegenerative diseases
.
In March 2022, AbbVie acquired Syndesi for $1 billion
Therapeutics
。 Syndesi's fastest-advancing SDI-118 is used to treat cognitive problems
in patients with AD and other cognitive impairments.
According to the company's website, AbbVie has a total of 9 CNS programs, 3 for the treatment of AD
.
In June 2021, BMS entered into an R&D cooperation with Prothena, and BMS obtained the US development rights
to PRX005, the Tau protein antibody therapy under development in Prothena.
Currently, there are 4 CNS products in the BMS pipeline, PRX005 and EVT8683 for neurodegenerative diseases, the latter licensed from Evotec
.
Pfizer, which announced the end of all CNS projects such as AD and Parkinson's in 2018, has obviously returned the most, but the direction of attention has changed
.
The $11.
6 billion acquisition of Biohaven resulted in the most blockbuster product being the migraine drug Nurtec, which officially went on sale
in March 2020.
In fact, Pfizer's interest in Nurtec is even earlier, and in November 2021, Pfizer has reached a strategic cooperation with Biohaven to acquire a total of $1.
24 billion for the commercialization rights
of Nurtec and the small molecule CGRP receptor antagonist zavegepant.
Amgen, which withdrew from the CNS field in 2019, re-intervened in a more special
way.
It was founded with ARCH Venture Partners ($400 million) in 2021 with a US$100 million investment
Neumora
Therapeutics
。 Neumora, which focuses on precision medicine for brain diseases, was founded as an asset
of three of ARCH's startups and two companies.
Amgen has also reached a development cooperation with Neumora: Neumora has introduced global interests in two of Amgen's CNS projects, targeting casein kinase 1δ and glucocerebrosidase; Neumora also collaborates with Amgen's deCODE Genetics Center
.
For Amgen, investment coupled with license out of its own pipeline is a more manageable strategy
.
New technologies and multiple targets
New technologies and multiple targetsIn these recent CNS R&D collaborations, cutting-edge technologies are becoming more and more sought
after.
Of more interest are gene therapy and nucleic acid drugs, and there are 5 related collaborations
.
The five collaborations cover different directions, including adeno-associated virus (AAV) vector gene therapy, gene editing, RNA editing, siRNA, and antisense oligonucleotide drugs
.
A large part of collaboration in the field of gene therapy is solving tissue-specific delivery problems
.
Novartis and Voyager, Biogen and Capsigen, two collaborations related to AAV gene therapy, are to find viral vectors more suitable for central nervous system delivery; Lilly's collaboration with Evox focuses on RNA drugs, and the collaboration also revolves around delivering RNA drugs
using Evox's exosome technology on delivery systems.
Biogen has another collaboration with Sangamo focused on gene editing, including ST-501 (tau-related diseases such as AD), ST-502 (synucleinopathy such as Parkinson's), and 10 undisclosed projects (1 neuromuscular disease, 9 CNS fields).
Sangamo has developed a zinc finger nuclease gene editing technology platform, and mostly cooperates
with big pharmaceutical companies.
Roche's collaboration with Shape is about RNA editing
.
RNA editing is a hot "rookie" in the field of gene editing in recent years, compared with DNA editing, the effect of RNA editing is not permanent, there may be better security, many companies are laying out this direction
.
In addition to the application of new technologies such as gene therapy, it can also be observed that the cooperation of projects in the same disease field has a relatively diverse target selection
.
Due to unknown pathogenic mechanisms, lack of biomarkers, blood-brain barrier, and difficult clinical design, CNS drug research and development has been difficult and ineffective
.
Compared with the earlier years when the industry rushed to the mechanism of amyloidosis, the multi-dimensional and multi-directional layout, the introduction of new technologies and new targets may be a wiser and risk-reducing choice
.
