The capital window for RNAi is reopening.

On October 16th local time, City Therapeutics, a small nucleic acid emerging company that has only been established for three years, landed on the US stock market with an IPO price of $18 per share. After opening, the stock price rose 24% to $22.4, with a market value of over $1.1 billion.

City was co founded by John Maraganore, a legendary figure in the RNAi industry - the founder and former CEO of Alnylam Pharmaceuticals, who led the commercialization of Onpattro, the world's first RNAi therapy. In addition, City management and R&D team members have been involved in the development or commercialization of 7 of the 8 RNAi therapies approved by the FDA so far.

Of course, City is not the only RNAi company that has been sought after by capital this autumn.

At the end of September, another emerging small nucleic acid testing company, ADARx Pharmaceuticals, completed a larger IPO, opening at $22.10 per share on the first day, an increase of 30%, with a market value of approximately $2.1 billion. The two founders of ADARx were also born from another small nucleic acid testing giant, Arrowhead.

Looking at the two companies together, a clear commonality emerges: they both have no product revenue and are losing money, but they have gained entry to the public market through their star teams and differentiated platforms.

With the maturity of liver delivery, the RNAi industry has gone through the initial verification stage of whether it can be used as a drug. After this round of IPO window opens, what is the capital market really betting on?

01. Certainty and platformization imagination

The true potential of RNAi lies in its ability to target pathogenic genes in any organ. Diseases in the eyes, central nervous system, adipose tissue, and muscles are currently beyond the reach of RNAi due to the lack of effective delivery tools.

The pipeline design of City essentially combines certainty and imagination.

The fastest progressing pipeline CITY-FXI targets coagulation protein Factor XI. Like other Factor XI targeted drugs under development, this candidate drug aims to prevent "thromboembolic diseases" - situations where blood clots form, detach, and cause harm. At the same time, it should also be able to reduce the risk of bleeding, which is a safety hazard of existing drugs.

City plans to develop multiple indications for this therapy, including secondary stroke prevention, atrial fibrillation, and cancer-related thrombosis. Phase I trials have shown that the drug can reduce Factor XI levels by up to 85%. The company expects to launch its first phase II trial next year, which will include patients at high risk of thrombosis after knee replacement surgery.

Another pipeline, CITY-RBP4, targets eye diseases, with Stargardt's disease being the most common hereditary macular degeneration in children and adolescents. With over 30000 patients in the United States, CITY-RBP4 produces the gene RBP4 (a protein that transports vitamin A to the eyes) through silencing.

The drug will enter phase I clinical trials later this year, with results expected to be available in 2027. City is also exploring the application of CITY-RBP4 in other eye diseases, including map like atrophy.

The third project of City targets a particularly common type of anemia, which is caused by chronic inflammation triggered by long-term illness. It is reported that this "chronic anemia" affects over 5 million people in the United States, and an early study will be launched in 2027. City may also test the drug in other diseases with high incidence of anemia in the future, such as chronic kidney disease.

Overall, City has pushed three self-developed pipelines to the clinical stage, all of which are mature GalNAc liver targeting technologies. The true carrier of the platform's story is cityRNA, a trigger molecule that is about 30% shorter and has about one-third less negative charge than traditional siRNA.

In the current situation where liver targets have become a "red ocean", the core selling point of this set of molecules lies in the engineering breakthrough of extrahepatic delivery: smaller size and lower charge density mean better tissue penetration and endosome escape efficiency; By simultaneously utilizing the abilities of AGO2 and AGO3, we attempt to address the fatal weakness of traditional siRNA in low load utilization in extrahepatic cells. In conjunction with LRP1 ligands developed for the eyes, CNS, and adipose tissue, City attempted to demonstrate its success in replicating GalNAc outside of the liver.

This platform narrative has gained initial industry endorsement: in the field of ophthalmology, City has reached a cooperation agreement with Bausch&Lomb; In the central nervous system, in collaboration with Bojian, the potential milestone total is about 1 billion US dollars. Two transactions injected the credit endorsement of major pharmaceutical companies into City's blueprint for extrahepatic delivery.

However, endorsement cannot replace data, and the platform itself is still in the preclinical validation stage - which constitutes the core contradiction of City's current valuation: the capital market is willing to pay a premium for the long-term imagination of "extrahepatic delivery", but this premium can only be proven reasonable when CityRNA truly runs as low as the liver target in human tissue.

02. "Alnylam 2.0" Halo

City originally planned to issue 9.72 million shares, but actually issued 11.11 million shares, raising funds from approximately $175 million to $200 million. The key to its ability to obtain oversubscription and expand its issuance scale without income or later clinical assets lies in its people.

You should know that John Maraganore is the most recognizable name in the field of RNAi. As the founding CEO of Alnylam, he took nearly two decades to bring RNAi from being questioned as "untreatable" to the commercialization stage of multiple FDA approved products.

Tracy Zimmermann, the Chief Scientific Officer of City, also comes from Alnylam and is the first author of a Nature paper in 2006 that first demonstrated the gene silencing effect of RNAi in non-human primates. She is also the co inventor of Amvuttra, the first blockbuster product in the field of small nucleic acids.

As for City CEO Andy Orth, he was responsible for the commercial listing of Onpattro, Givlaari, and Oxlumo at Alnylam. City stated in its prospectus that its team has been involved in the discovery, development, or commercialization of seven of the eight RNAi therapies approved by the FDA to date.

The value of this "Alnylam 2.0" resume halo has already been quantified by the primary market. City has accumulated approximately $238.8 million in equity financing before completing its IPO, with a Series B investment of $99.5 million bringing in Viking Global and Sofinnova. ARCH Venture, Fidelity, and Invus have also continued to raise funds.
However, despite its numerous accolades, from a financial data perspective, City has always been in a state of loss.

As of June 30, 2026, City had a net loss of $53.4 million in the first half of the year, more than double the $24.3 million in the same period in 2025; The research and development expenses increased from $24.4 million to $46.3 million, with a cumulative deficit of $142.5 million.

As of the end of the first half of the year, City's cash and equivalents on the books were $172.1 million, and with the net proceeds from the IPO, the company is expected to support operations until the end of 2028.

For a company that was only established in July 2023 and has no product revenue, such a burning speed of money is not surprising. Looking at it from a different perspective, this IPO raising $200 million is actually buying a data validation window for the next two years. If solid clinical data cannot be obtained by then, no matter how bright the halo is, the pressure of finding new money cannot be avoided.

03. Different paths leading to the same destination under the "halo effect"

To some extent, City's IPO was driven by another company.

On September 25th, ADARx Pharmaceuticals was listed on NASDAQ with a top price of $17 and a total fundraising of $446.3 million, an increase of about 20% from the original plan. On the first day of listing, it opened at $22.10, up 30% from the issue price, and closed at $19.35, up 13.8%. Its market value is $1.978 billion based on the closing price.

Worth noting timeline: ADARx publicly submitted its prospectus on September 4th, only about three weeks into listing, reflecting the fast-paced pace of off market pricing negotiations.

In the window where biotechnology IPOs in 2026 generally rely on "late stage assets+deterministic data", ADARx has become a landmark sample of the new round of capital attention recovery in the RNAi track - BioCentury statistics show that its first day performance directly drove multiple biotechnology companies such as City and Iambic to submit S-1 intensively in the following days.

Like City, the founding team of ADARx also comes from a prestigious family: CEO Li Zhen previously served as Arrowhead's Senior Vice President for Chemistry and Non Clinical Development, and previously served as the Director of Chemistry for RNAi Therapy and Process Chemistry at Merck; Co founder Rui Zhu is also from Arrowhead.

In terms of pipeline development progress, ADARx is slightly ahead of City.

Its core asset, onvuzosiran (PKK siRNA), has entered Phase III clinical registration for hereditary angioedema (HAE). Phase I data shows a maximum decrease of approximately 93% in plasma kallikrein (PKK). The company expects to obtain preliminary data by the end of 2027, and if the results are positive, it is expected to submit a marketing application to the FDA in 2028.

Another core pipeline, agazisiran, showcases the charm of platform assets. It targets complement factor B (CFB), which is involved in the complement pathway of the immune system and is associated with various complement mediated diseases.

ADARx has not limited it to a single indication, but is simultaneously advancing three Phase II clinical trials, covering kidney diseases such as IgA nephropathy and C3 glomerulopathy, paroxysmal nocturnal hemoglobinuria (PNH), and map like atrophy (GA) secondary to age-related macular degeneration. Preliminary Phase II data is expected to be released in the second half of 2027.

In addition, ADARx has also deployed ADX-077 targeting adipose tissue (reducing fat while preserving muscle, complementary to GLP-1 rather than replacing it) and ADX-199 crossing the blood-brain barrier (reducing amyloid production from the source) in preclinical settings. Its extrahepatic ambitions are similar to City's, but more advanced.
The pricing logic of ADARx is not only based on pipeline progress, but also on the validated 'industrial capital endorsement chain'.

The total amount of the option based cooperation previously reached between AbbVie and ADARx is approximately 8.17 billion US dollars, and this transaction does not include ADARx's five core pipelines, but covers new targets in the fields of neurology, immunology, and oncology - in other words, AbbVie is not buying a pipeline, but ADARx's platform expansion capabilities.

In this IPO, AbbVie also participated in a $89 million private placement and held approximately 4.9% of the outstanding shares, raising a total of $535.3 million through IPO and private placement.

Combining the above factors, when looking at the two IPOs together, the pricing logic of capital for both is highly consistent: what is bought is not the current pipeline value, but the execution ability of "verified people" in "unverified directions" and the credit endorsement of giants.

But the risks are equally consistent: the patience of the capital market is extremely limited, and past achievements and endorsements from giants will quickly give way to the assets themselves in the face of key clinical data.
The celebrity halo is essentially an advance credit limit. City ultimately needs to prove that the extrahepatic delivery of cityRNA in the human body is not just a theoretical concept; ADARx will have to overcome the efficacy and convenience test of Onvuzosiran in HAE Phase III clinical trials.

Getting a ticket to the IPO is just the first step, and they need to answer the same cruel question: when the story is finished and the data appears, can the pipeline fight on its own?

The popularity of small nucleic acids ultimately boils down to a simpler question: whether delivery can cover more tissues, whether clinical trials can provide reproducible benefits, and whether industrialization can turn "one shot drug delivery" into stable delivery.

On November 27-28, 2026, the 17th Taizhou Pharmaceutical Expo, hosted by Taizhou Pharmaceutical City Guotai Exhibition Co., Ltd. and co organized by Tong Xieyi, will be held at the China Pharmaceutical City Convention and Exhibition Center. The theme of this year's Medical Expo is "Gathering Strength, Innovating, Transforming and Empowering Health with New Quality". The planned exhibition area is 30000 square meters, with one opening ceremony, seven core exhibition areas, and about 20 special events.

Among them, the "Innovation and Development of Small Nucleic Acid Drugs" thematic docking and exchange activity will focus on differentiated target selection, breakthroughs in extrahepatic delivery, clinical development strategies, and platform based BD pathways. When capital begins to ask 'where is the next product', the answer to the small nucleic acid test is not in the number of pipelines, but at the intersection of delivery boundaries, clinical evidence, and industrialization capabilities.

References:
1. Prospectus of City and ADARx
2.IPO Bonanza，City Therapeutics Files for IPO: Maraganore's Next RNAi Bet
3. Arterial network, the team has participated in the development of 7 approved RNAi drugs, and this emerging small nucleic acid company is striving for IPO
Backed by a BD of 481 million US dollars, the emerging small nucleic acid team from Peking University and Tsinghua University is sprinting towards IPO