9Month3Day, Argo (hereinafter referred to as“Argo”) Announced a new strategic cooperation with Novartis to jointly develop treatments for cardiovascular diseases.siRNADrug. This collaboration is between the two parties from last year1The deepening of the first cooperation in the month, according to the agreement,Argo will obtain1.6USD billion upfront payment, with a total potential milestone of up to52Billion US dollars. Adding to the previous collaboration41.65"Billion US dollars,"The Potential Total Amount of the Two Transactions is Nearly 10 Billion, Setting a New Record“Astronomical Price”BD。

And just9Month2The other day, Novartis had just announced that22Billion USD (2USD billion upfront payment) withArrowhead PharmaceuticalsReach cooperation, the latter's preclinicalsiRNADrugARO-SNCAThe global exclusive rights for development, production, and commercialization were secured for the treatment of Parkinson's and other synucleinopathies. The very next day, they continued to intensify their efforts, choosing to expand the scope of cooperation with Argo, aiming at multiple assets across various stages in the cardiovascular field. This reflects,It is not only the favorability towards Argo's technology platform and pipeline, but also Novartis' increased investment.siRNAStrategic Intent。

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From“Buy Fish”To“Recognize Fish”

The core标的of this transaction mainly includes oneⅡPeriodsiRNAPriority negotiation rights for drugs, options for the rights outside of China for two early molecules, and one preclinicalsiRNAExclusive License Outside of China for the Drug。

First, the two parties will jointly exploreBW-00112（ANGPTL3) Combination therapy for the treatment of dyslipidemia. This product is currently inII In the phase of clinical trials, the subsequent clinical trials for combination therapy will be led by Argo. Novartis will gain the preferential negotiation rights for this product. Meanwhile, Argo will also grant Novartis the option for rights outside of China for two molecules in the early research stage, intended for the treatment of severe hypertriglyceridemia.(sHTG) And mixed dyslipidemia. As for another drug candidate in the preclinical research stage,siRNA For the candidate drug, Novartis will obtain exclusive rights outside of China, including profit and loss sharing in the United States and China.(P&L) The mutual option, expected2026 Will launch in the yearI Phase clinical trial.

The scope of cooperation covers multiple stages in a packaged manner, meaning that it is based on existing achievements,Argo's continuous development and discovery of high-quality candidate platform capabilities have also been acquired.MNCApproval, and the trading model, which is not short of highlights, also provides great support for the progress of both parties. Through options and preferential negotiation rights, Novartis has retained decision-making flexibility, locking in multiple future options in advance at a relatively controllable cost, while in both China and the USP＆LThe reciprocal option also helps Argo retain the possibility of participating in the commercialization and profit-sharing of the two largest pharmaceutical markets.

Looking back at the initial connection between the two, at that time Argo granted Novartis two cardiovascularsiRNAOverseas rights of the drug, including oneIGlobal rights for Phase clinical products and oneI/IIaThe rights outside Greater China for the product in question, with a special provision in the agreement that Novartis retains.“The Most Extra for Cardiovascular Diseases2Option for Target Compounds”. The new agreement involvessiRNAThe candidate molecule falls within the scope of this option. According to reports, the core pipeline in the first collaborationBW-00163(HypertensionsiRNA) has been this year6Monthly EntryⅡThe Phase clinical trial successfully triggered the milestone payment, laying the foundation for this deepened cooperation.

It is worth noting that,Compared to common prepayments+Milestone Payments+The model of sales sharing. On the basis of R&D cooperation, this transaction also includes an equity investment intention, further deepening the binding of interests and strategic recognition between the two parties.According to the news disclosed on Argo's official website, Novartis has expressed preliminary interest in participating in its next round of equity financing. The specific participation (including investment amount and timing) still requires routine due diligence and will be determined through negotiations and the signing of a formal agreement by both parties.

It can be seen that after the initial trial, both parties have established a good mutual trust. Argo's technical strength and R&D potential have continued to be highly regarded by Novartis, genuinely earning their favor once again and deepening the cooperation.

Why Argo?

Small Nucleic Acid Drugs(Oligonucleotide drugs,oligonucleotide) Refers to a length less than30ntOligonucleotide sequences, including various mechanisms and types, such as small interferingRNA（siRNA), minimalRNA（microRNAOrmiRNA）、ASO(Antisense Oligonucleotides),Aptamer(Nucleic Acid Aptamer) andCpGOligonucleotide (CpG ODN), throughRNAInterference (RNA interference, RNAi) Exerting pharmacological effects, it can selectively restrict targets with high specificity. It is not limited by the druggability of traditional protein targets and theoretically can target any pathogenic gene.

But in the early stages, due to susceptibility to nuclease degradation and high renal clearance, small nucleic acid drugs faced significant development challenges. Among them,siRNAAlthough drugs have attracted more capital and R&D investment due to their potential for higher efficiency and precision in gene regulation, the clinical translation of their technology is stillAlnylam、Ionisetc.biotechThe rapid rise and the industry's first wave of enthusiasm soon hit a bottleneck.

ForRNABased onsiRNAFor drugs, the delivery system is crucial. Delivery platforms that overcome major challenges such as systemic circulation, extravasation, tissue penetration, cellular uptake, and endosomal escape are vital in the field of small nucleic acids.“Chokepoint”Technology is also a necessary condition for the success of such drugs.How to Degrade EasilysiRNASafe and effective delivery to specific tissues or organs (other than the liver) has become a key obstacle.At that time, withAlnylam、Arrowhead、DicernaCompanies like Argo Biopharma as key representatives, multiple pharmaceutical enterprises continueImproving delivery systems and chemical modification technologies, promotingGalNac（N-Acetylgalactosamine) conjugation technology is mature, utilizing highly expressedASGPRReceptor achieves efficient liver targeting, breaking through the hepatic delivery challenge and drivingsiRNAField Self2016Entering the Harvest Period YearIn recent years, it has gradually covered a wider range of disease spectra, replacing or supplementing existing therapies in certain fields, with application areas expanding from early rare diseases to common chronic conditions such as cardiovascular and metabolic diseases.——For this kind of disease that requires long-term management, long-acting and low-frequency dosingsiRNAThe drug can be said to have all the advantages.

Currently,Extrahepatic Delivery(such as targeting the central nervous system, kidneys, muscles, and other tissues) remain critical challenges yet to be addressed. Overall,The delivery system also remainssiRNACore barriers in the field. It can be said that,Enhancing delivery capabilities and mastering delivery platforms are the key to achieving a technological moat.. It is precisely because of this that, with its innovative delivery platform, as well as the team's expertise in nucleic acid sequence design, chemical modification,GalNAcRich experience in the entire process of delivery technology, extracellular delivery technology, etc., focusing onsiRNAAlthough Argo was established less than5Years, but quickly caught up in a short period of time, successfully building a certain technical barrier. After the initial cooperation, they gained further recognition based on their R&D capabilities.MNCFavor.

Argo has established a complete nucleic acid drug development platform and, based on this, developed a diversified drug R&D pipeline covering various diseases. Its self-innovative constructionsiRNAThe name of the technology platform isRADS（RNA with superior Activity, Durability, Safety), that isPossess“Stronger Activity, Longer Efficacy, Higher Safety”TheRNAMolecular Platform. After rapid construction, every2-3months or so, that is, the completion of targeting a specific targetsiRNA, for exampleAGT、HBV、LPA、PKK、C3、XDHThesiRNA，Excellent screening and optimization capabilities。

ThroughsiRNASequence design, chemical modification, and optimization of delivery methods, the platformSignificantly improvedsiRNAEfficacy and stability of the drug, reducing dosing frequency and side effects, which can develop drugs with better efficacy at lower doses and longer duration, with the potential to achieve once-a-year dosing for certain indications, has yielded positive results in multiple clinical trials.More crucially, forsiRNAFor drugs, once a mature technology platform is established, the speed of developing similar drugs will significantly increase, enabling a shorter drug development cycle (typically3-5Years) and a higher success rate, is expected to achieve consecutive significant breakthroughs and receive sustained favorable attitudes, which is not hard to imagine.

Focusing on the field of cardiometabolic diseases, althoughAlnylam、ArrowheadCompanies such as Argo Biopharma have already made early investments.PCSK9、ANGPTL3、LPA、AGTSuch as targetsRNAiDrugs (some projects have entered the late-stage clinical trials or been marketed). Argo has achieved rapid follow-up and even simultaneous development for the same target by leveraging its own technology platform.

Figure1 ArgoRANiTechnology PlatformRADS

In addition, itsCore TeamIs also a key factor in this cooperation.Chairman andCEOShu DongxuDr. once worked atArrowhead`, leading the development of extrahepatic delivery platforms, with a background in chemistry from Peking University and overseas postdoctoral research;`Chief Scientific Officer Pengcheng ShaoDr. has nearly17Years of experience in medicinal chemistry, formerArrowheadDirector of Medicinal Chemistry, participating in projects across multiple fields including cardiovascular, diabetes, oncology, and central nervous system;Chief Medical Officer Dr. Jin JianjunFormerly served as the head of clinical development at Novartis China, leading the world's first approved treatment for chronic diseases.siRNADrugInclisiran（Leqvio) in AsiaIIIPhase Research;Chief Business OfficerPatrick GallagherPossess25Years of investment experience, with a cumulative completion of approximately10Hundreds of millions of dollars in funding, having led multiple international mergers, acquisitions, and cooperation projects. This international team provides a solid foundation for Argo to quickly establish a technology platform, advance pipelines, and achieve international cooperation.

Currently, Argo has6PaymentRNAiCandidate drugs enter clinical research, coveringCardio-cerebrovascular diseases, viral infections, metabolic diseases, and rare diseasesIn multiple treatment areas.

Table1 Argo Biopharma Clinical Pipeline Statistics

And for Novartis, the reason behind the lavish spending,It is precisely because ofsiRNAA powerful boost to its cardiovascular pipeline.

2024In the year, the cardiovascular field contributed to Novartis21% of sales, up to78billion dollars, becoming another major performance driver outside of oncology, with a high15% comes from its blockbuster productEntresto. However,EntrestoThe patent was granted this year7Month of expiration,FDAWith the approval of generic drugs, many European and American pharmaceutical companies have long been prepared to seize market share. Chinese pharmaceutical companies such as Salubris, Shijiazhuang Pharma Ouyi, and Zhengdatianqing have also made early arrangements and are waiting for the right moment to act. Institutions predict that the listing of generic drugs...3Will be divided within months85％-90% of the market share, causing billions in losses. At the same time,2019In a year, Novartis invested a huge sum of money in97Billion-dollar acquisition ofLeqivo(The first and only lipid-lowering drug approved for marketingsiRNADrug sales have still not met expectations, and while they have contributed to some performance, they are unable to fill the gap.EntrestoThe performance gap caused by the loss of patent protection, and the ramp-up speed has already slowed down.

And exceptEntrestoIn addition, several other key products from Novartis will also be...2030Facing a patent cliff before the year, including2027Expired in ...Promacta(Platelet Boost) andKisqali（CDK4/6），2029Expired in yearsCosentyx（IL-17) and2030Expired in yearsKesimpta（CD20）。

Thus,Finding the next cardiovascular drug that can support billions of dollars in sales and fill the growth gap in the cardiovascular field has become a critical question that Novartis urgently needs to address. By leveragingsiRNAThe broad prospects of drugs, expanding pipelines, and long-term planning in other core areas are also important considerations that cannot be overlooked.。

In recent years, Novartis has focused on its strengths in cardiovascular, neuroscience, and immunology. Internally, it emphasizes advancing core projects, while externally, it prioritizes acquiring reserve technologies and new molecular entities, actively promoting a transformation from internal R&D to external sourcing.48 Two consecutive transactions within hours“Lightning Trade”This well supports this strategic move. AndArrowheadCollaborating on preclinical pipelines is not only about betting on high-quality pipelines but also aims to leverage them.TRiMThe R&D potential of the platform will advance the overall progress of intractable neurodegenerative diseases such as Parkinson's disease. Through collaboration with Argo, Novartis will be able to access multi-stage, highly promising cardiovascular therapies based on flexible decision-making.siRNADrugs, rapidly strengthen the existing layout while securing high-quality pipelines for the future.

This cooperation is not only a win-win, but alsoMarks the innovation in drug research and development in ChinaRNAiThe frontier has reached international standards.. Currently, the industry has formed withAlnylan、Ionis、SareptaAt the core of the fiercely competitive landscape, continuously leading industry innovation, Novartis, Pfizer, Roche, and othersMNCThrough cooperation and acquisitions, they have taken the lead in strategic layout and deep participation. Nevertheless, with robust technological platform innovation and continuous R&D investment, emerging forces in China's pharmaceutical industry can still catch up. Moving beyond simple product transaction models, they are taking the lead in subsequent trials, becoming sources of innovation, and participating in global market competition, which is truly encouraging.

Reference:

1.News and Public Information from Argo's Official Website

2.ArrowheadOfficial Website News

3.https://mp.weixin.qq.com/s/qicDfsHRm-tQhbyNmgMiIA

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