RNA Therapeutics

Shares of Moderna and Novavax rose today after The New York Times reported that the US National Institutes of Health, or NIH, plans to launch a public-private partnership to accelerate the development of personalized cancer vaccines. The vaccine project is expected to begin in December, focusing on pancreatic cancer, liver cancer, and colorectal cancer, as well as certain tumors in children. Previous trials have used mRNA technology to train the body's immune system to recognize and attack proteins specific to cancer cells. The positive reaction to the news was most evident for Moderna, which is developing personalized mRNA cancer vaccines together with Merck. Moderna's share price has soared more than 600% since the start of this year, making it the best-performing stock among the companies used to calculate the S&P 500 index.

Asahi Kasei Therapeutics, the global specialty pharmaceutical business of Tokyo-based Asahi Kasei, announced that the first patient has been dosed in a randomized Phase 2a clinical trial evaluating AIC468, a novel antiviral antisense oligonucleotide, in adult kidney transplant recipients with BK virus infection. The trial, registered as NCT07503561, is a randomized, double-blind, placebo-controlled study and forms part of a larger Phase 2/3 program designed to assess safety, tolerability, and pharmacokinetic profile across multiple dose levels, measured by the frequency and severity of treatment-emergent adverse events. Progression into Phase 2a was supported by favorable Phase 1 safety, tolerability, and pharmacokinetic data, and the investigational program was developed by Aicuris Anti-infective Cures AG, which is now part of Asahi Kasei Therapeutics. Carl Kraus, Chief Medical Officer of Asahi Kasei Therapeutics, said BK virus reactivation remains a major complication for kidney transplant recipients that can lead to graft dysfunction and BK nephropathy, and that dosing the first patient represents an important step toward a targeted antiviral therapy for a community with no approved treatment options. BK virus-associated nephropathy affects up to 10% of kidney transplant recipients and can result in graft loss, while current management relies on reducing immunosuppressive therapy, which increases the risk of graft rejection.

Moderna will join the Nasdaq-100 Index on Oct. 9, replacing Warner Bros. Discovery before the opening bell on Friday. The swap follows the completion of Paramount's acquisition of Warner Bros. Discovery, whose shares have ceased trading; the combined entity is now named Skydance and trades on the NYSE under the ticker SKYD. Nasdaq did not cite a specific reason for adding Moderna, but the inclusion follows a sharp rise in the company's market value and growing optimism around its prospects, supported by positive phase III results for its personalized cancer therapy developed with Merck, which met its primary endpoint of recurrence-free survival and a key secondary endpoint of distant metastasis-free survival in certain high-risk melanoma patients. The Nasdaq-100 is tracked by more than 200 investment products with over $800 billion in assets under management globally, so index funds adjusting their portfolios could create incremental institutional demand for Moderna shares. The inclusion does not change Moderna's underlying fundamentals, operations, cash flow or pipeline development, and the stock's longer-term performance will continue to depend on its business and pipeline. Moderna shares have skyrocketed 566% year-to-date, far outpacing the industry's 1% growth, and the stock trades at 30.84 times forward 12-month sales on a price-to-sales basis versus an industry average of 2.06 times.

GSK has entered a collaboration with Wave Life Sciences to advance a GalNAc-siRNA hepatology candidate into its development pipeline, while separately expanding its tuberculosis research with AN2 Therapeutics. The Wave Life Sciences partnership focuses on RNA-based therapies targeting liver diseases using GalNAc-siRNA technology, giving GSK another modality in liver disease and access to Wave's SpiNA design platform without building that RNA chemistry capability internally. The AN2 Therapeutics work is supported by new funding from the Bill & Melinda Gates Foundation for boron-based drug discovery. The Wave hepatology move and the Gates-backed TB research funding sit within GSK's existing narrative of heavier R&D reinvestment and business development, though the high R&D spend and execution uncertainty still apply if these programs move slowly or fail to produce strong late-stage assets. The clearest next marker will be whether GSK or Wave disclose that one of the three remaining collaboration programs reaches formal candidate selection over the next research updates, triggering further milestone payments.

Lepu Medical announced that its controlling subsidiary, Shanghai Minwei Biotechnology, has received a notice from the US FDA agreeing to allow clinical trials for the MWN117 injection. The drug is an siRNA therapy targeting INHBE inhibition, indicated for overweight and obesity, and has already received clinical trial approval from China's CDE. Non-clinical studies show that the drug, used alone or in combination with GLP-1 receptor agonists, effectively reduces body weight and body fat while reducing muscle loss, with efficacy lasting up to 12 weeks. Currently, no similar drug has been approved for marketing domestically or internationally.

Madrigal Pharmaceuticals reported in the Journal of Hepatology that a pre-specified secondary analysis of the Phase 3 MAESTRO-NASH trial found Rezdiffra, also known as resmetirom, improved fibrosis, MASH resolution, liver fat and biomarker levels across patients regardless of common genetic risk variants including PNPLA3, HSD17B13, TM6SF2, MTARC1 and MBOAT7, with safety consistent with the overall study. The company said Rezdiffra's thyroid hormone receptor-beta mechanism appeared unaffected by these genetic risk pathways, suggesting the drug's benefit may extend broadly across genetically diverse MASH populations. Madrigal is also pursuing a precision-medicine PNPLA3 siRNA program, having recently added MGL-0795, a PNPLA3-targeting siRNA, to its pipeline alongside the existing Pfizer DGAT2 combo program. The company's narrative projects $3.2 billion in revenue and $935.6 million in earnings by 2029, requiring 42.0% yearly revenue growth and about a $1.25 billion earnings increase from -$309.4 million today, while more optimistic analysts assume about US$3.6 billion in revenue and US$1.5 billion in earnings by 2028.

Tempus announced an expanded, multi-year collaboration with Moderna and Merck to support the potential commercialization of intismeran autogene, also known as V940 or mRNA-4157, a potential first-in-class individualized neoantigen therapy being evaluated in combination with KEYTRUDA in patients with completely resected stage IIB-IV melanoma and other cancer types. Intismeran autogene is jointly developed by Moderna and Merck, known as MSD outside the United States and Canada, and the new collaboration builds on joint efforts initiated last year. Under the agreement, Tempus will manage the timely collection and transfer of tumor tissue and blood samples required for next-generation sequencing, and, subject to applicable regulatory approvals, will also provide NGS services to support the intismeran autogene design and manufacturing process. Financial terms of the collaboration were not disclosed. Moderna Chief Business Officer Said Francis said the partnership lets the company leverage Tempus's commercial footprint and advanced sequencing capabilities, while Jannie Oosthuizen, President of Global Oncology and MSD International, said such collaborations are helping build the infrastructure needed to bring individualized neoantigen therapies to patients at scale.

Therna Biosciences appointed Kevin Green, former Chief Business Officer of Inceptive, as Chief Operating Officer and added two AI technical leaders to its advisory team, while the NIH Common Fund selected the company as a Phase I winner of its Targeting RNA in Disease with Novel Technologies Challenge. Green, who joined Therna in August and brings more than 20 years of experience across AI-enabled drug discovery and RNA therapeutics, leads the company's operations and business development as its RNA-Logix platform moves into partnered and internal programs. The new AI advisors are Dr. Dave Burke, the first Chief Technology Officer of Arc Institute and previously Vice President of Engineering for Android at Google, and Mr. Harsh Mehta, co-founder and CTO of Mirendil and previously a Senior Research Scientist at Anthropic and a researcher at Google. Therna is one of 25 Phase I winners of the three-phase TRDNT Challenge, which offers up to $13.1 million in total awards as teams develop and validate their technologies through 2027. Therna's winning proposal introduces a co-scientist agent built on RNA-Logix that designs and optimizes sequence-specific activating antisense oligonucleotides for ultra-rare haploinsufficiencies.

Novartis entered a licensing and option agreement with China-based Abogen Biosciences, giving the Swiss pharma giant exclusive worldwide rights to Abogen's lead candidate ABO2203 and options to license additional programs built on Abogen's proprietary RNA platform. Under the agreement, Abogen will receive an upfront payment of $575 million and is eligible to receive up to approximately $7.2 billion in potential milestone payments if all options covering additional programs are exercised and the specified development, regulatory and commercial milestones are achieved, plus royalties on future product sales. ABO2203 is an investigational messenger RNA-encoded CD19xCD3 T-cell engager being developed for autoimmune diseases, designed to reset B cells by directing endogenous production of T-cell engagers in vivo. The transaction remains subject to customary closing conditions, including required regulatory clearances. The deal comes as Novartis faces generic competition for Entresto and Promacta and back-to-back pipeline setbacks, including the late-stage failure of pelacarsen and the HARBOR study of del-desiran in myotonic dystrophy type 1.

Nasdaq said Thursday that Moderna will become a component of the Nasdaq-100 Index, replacing Warner Bros. Discovery before market open on Friday, October 9. The vaccine maker's shares have jumped more than sixfold this year to a valuation of roughly $75B. Warner Bros. Discovery is also set to be removed from major indexes, including those tracked by MSCI and S&P, as its merger with Paramount Skydance is expected to close on October 6 following a months-long delay.

Aptadir Therapeutics has closed a EUR 40M Seed round to advance a novel class of RNA inhibitor-based therapeutics for intractable genetic conditions. The round was led by 4BIO Capital, with follow-on participation from the company's original pre-seed investor EXTEND, Italy's National Technology Transfer Hub launched by CDP Venture Capital SGR and jointly funded by Angelini Ventures and Evotec SE. Additional support came from CDP Venture Capital through the Digital Transition Fund, Indaco Venture Partners, XGEN Venture, CE-Ventures, Angelini Ventures through a direct investment, Kerna Ventures, Italian Angels for Biotech, and Club degli Investitori. The funds will advance the company's pipeline of disease-modifying investigational RNA therapeutics, including its lead candidate CAP1-FMR1 for Fragile X Syndrome, based on a new class of RNAs called DNMTs Interacting RNAs that block aberrant DNA methylation at a single gene level to reactivate silenced gene expression. The science originates from the Beth Israel Deaconess Medical Center, the Italian Research National Council, and the Cancer Science Institute of Singapore.

ADARx Pharmaceuticals is seeking a valuation of as much as $1.74 billion in a US IPO that could raise up to $371.9 million. The San Diego-based RNA drug developer plans to offer 21.9 million shares at between $15 and $17 apiece and list on the Nasdaq under the ticker ADRX. AbbVie has agreed to invest up to $100 million through a concurrent private placement, which ADARx said would give AbbVie a roughly 4.9% stake following the IPO; AbbVie had previously paid ADARx $335 million in May 2025 as part of a research collaboration. Three of ADARx's experimental drugs are in clinical testing and another two are in advanced preclinical development, with its most advanced candidate, onvuzosiran, in late-stage testing for hereditary angioedema. IPOX Research Associate Lukas Muehlbauer described the AbbVie investment as external validation of ADARx's technology, though the valuation still rests on experimental medicines with no approved product.

Moderna and Merck reported that their Phase 3 INTerpath-001 trial of personalized cancer vaccine intismeran autogene plus Keytruda met its primary endpoint in melanoma, with full data presented earlier this month at the European Society for Medical Oncology Congress 2026. Moderna is also in talks with Middle East partners about potential investment and manufacturing cooperation, pairing its mRNA oncology push with efforts to extend its geographic footprint and industrial capabilities beyond its original COVID-19 franchise. The company recently won FDA approval of mFlusiva, its mRNA flu vaccine for adults 50 and older, underscoring its push to build a non-seasonal respiratory portfolio. Moderna's narrative projects $4.5 billion revenue and $782.2 million earnings by 2029, yielding a $119.56 fair value, a 40% downside to its current price, while some of the most optimistic analysts assume revenue could reach about US$8.5 billion and earnings turn positive by 2029.

Pfizer Canada and BioNTech announced Health Canada's approval of the Omicron XFG-adapted COMIRNATY vaccine for individuals aged 6 months and older, aligning with 2026-2027 public health recommendations. A few days earlier, BioNTech and OncoC4 reported that the investigational CTLA-4 antibody gotistobart nearly doubled median overall survival versus chemotherapy in a Phase 3 lung cancer trial stage. The Health Canada authorization, following earlier US and EU XFG approvals in 2026, shows the COVID-19 franchise still contributes regulated, seasonal revenue while BioNTech leans into oncology. BioNTech's narrative projects €2.2 billion revenue and €390.1 million earnings by 2029, implying a 6.0% yearly revenue decline and an earnings increase of about €2.1 billion from -€1.7 billion today, with a $118.06 fair value and 20% upside to its current price. Bullish analysts assume revenue climbs to about €3.0 billion and earnings to €313.1 million by 2029, though the new gotistobart data and oncology execution risks could shift how those upbeat assumptions are weighed against more cautious views.

Moderna has entered high-level investment talks with the UAE government covering advanced pharmaceutical manufacturing and research and development collaboration. The discussions focus on expanded research capabilities, potential local production, and broader access to Middle Eastern healthcare markets. Management framed the UAE engagement as part of a wider push to build out Moderna's international footprint beyond existing Western partnerships. The company, a large US biotech group with a market cap of about $79.4b, focuses on messenger RNA based medicines and has a history of working closely with public sector buyers. Investors will watch whether the talks turn into concrete agreements, such as a defined R&D center, a manufacturing investment figure, or a multi year vaccine procurement deal, and any link to the INTerpath-001 melanoma program or the mRNA respiratory portfolio.

Moderna Chairman Noubar Afeyan met UAE Minister of State Saeed bin Mubarak Al Hajeri, who also chairs the Emirates Drug Establishments, to discuss investment and cooperation in advanced pharmaceutical industries. The talks covered research and development collaboration, exchange of expertise, and strengthening the UAE's pharmaceutical manufacturing capabilities, building on the strategic partnership between the United States and the UAE. Moderna shares climbed to a record intra-day high of $195.71 before closing up 6.98 percent at $194.82 apiece. Investors are also awaiting an updated readout on the INTerpath-001 trial of intismeran autogene in combination with Merck's Keytruda, to be presented at the European Society for Medical Oncology Congress 2026 in Madrid from October 23 to 27, 2026. The phase 3 trial previously met its primary endpoint of recurrence-free survival and key secondary target of distant metastasis-free survival, marking the first positive phase 3 readout for a combination of individualized neoantigen therapy and mRNA-based cancer therapy. In the second quarter, 49 hedge funds held positions in Moderna, down from 52 in the first quarter, but their combined holdings rose 10 percent to $1.5 billion from $1.4 billion quarter-on-quarter.

Pfizer Inc. and BioNTech SE announced on August 27 that the U.S. FDA has approved the supplemental Biologics License Application for their 2026–2027 COVID-19 vaccine formula, COMIRNATY XFG. The updated formula targets the XFG variant and is authorized for adults aged 65 and older, as well as individuals aged 5 to 64 with high-risk underlying conditions. The approval, based on clinical, real-world, and manufacturing data showing strong immune responses against circulating strains, aligns with FDA strain guidance for fall 2026. For Pfizer, the clearance protects a recurring seasonal revenue stream that supports margins and cash flow while the company funds its non-COVID pipeline and manages upcoming loss-of-exclusivity events. For BioNTech, it validates the execution power of its proprietary mRNA platform and preserves its balance sheet, which carries minimal debt and substantial cash reserves to fund late-stage oncology trials without dilutive financing. Both companies still face long-term market contraction as COVID-19 booster demand has normalized well below pandemic peaks, leaving Pfizer's earnings less predictable against elevated debt and exposing BioNTech's heavy operating losses as vaccine revenues fall short of its massive R&D expenses.

Otsuka Pharmaceutical and U.S.-based Ionis Pharmaceuticals announced on the 22nd that their jointly developed treatment for hereditary amyotrophic lateral sclerosis, ulefnersen, met its primary goal in a late-stage clinical trial. In patients with FUS mutation ALS, a rare inherited form of ALS that damages the nerve cells controlling movement, ulefnersen improved function and extended survival compared with the placebo group. The drug reduced markers of nerve cell damage and slowed disease progression, and most side effects were mild or moderate, indicating a favorable safety profile. No approved treatment currently targets the genetic cause of FUS-ALS, and the two companies plan to discuss the results with the U.S. Food and Drug Administration and global health authorities as they explore a path toward accelerated approval. Separately, Otsuka Pharmaceutical has launched a global early access program for FUS-ALS patients unable to participate in the trial, allowing physicians to request access to ulefnersen before approval.

Arcturus Therapeutics said interim phase 2 results for ARCT-810 showed the candidate reduced and/or maintained first morning fasting ammonia within the normal range in patients with ornithine transcarbamylase deficiency, and also reduced glutamine, with some individuals reaching the normal range. Based on those results and a June meeting with the US FDA, the company aims to begin dosing of ARCT-2601 close to the end of the year in participants 12 years and older under an amended phase 2 protocol that integrates ARCT-2601 into the current ARCT-810 phase 2 study. Both ARCT-810 and ARCT-2601 are mRNA therapeutics for OTC deficiency, but ARCT-810 uses the LUNAR platform while ARCT-2601 uses the next-generation LUNAR 2.0 platform, which Arcturus says produces greater than 30-fold higher protein expression and could allow for lower or less frequent dosing. OTC deficiency is a rare genetic disorder in which the body stops breaking down and removing nitrogen, leading to dangerous ammonia levels in the blood. Arcturus is also acquiring AI discovery company myNeo, with which it has worked since 2024, and the deal is expected to close in October.

Roche Holding partner Ionis reported that sefaxersen met the primary endpoint in the Phase 3 IMAgINATION trial for IgA nephropathy, delivering a statistically significant reduction in proteinuria compared with placebo. The clinical win comes on top of a strong run for Roche Holding, with the share price up 8.32% over 90 days and 11.58% year to date, and a 1-year total shareholder return of 44.02%. Roche Holding now trades at CHF363.20, only about 3% below the average analyst target, yet screens at a roughly 59% discount to an intrinsic value estimate, while the most followed narrative fair value of CHF353.34 pegs the stock as 2.8% overvalued. The SWS DCF model points the opposite way, implying a future cash flow value of CHF893.70. The story could still change quickly if key Phase 3 programs disappoint or if biosimilar pressure on older blockbusters accelerates faster than expected.

Ionis Pharmaceuticals announced positive late-stage results from two partnered phase III programs. The FUSION study of ulefnersen in amyotrophic lateral sclerosis caused by mutations in the fused in sarcoma gene met its primary endpoint assessing functional impairment and survival at 72 weeks, with Ionis reporting the results as statistically significant without disclosing supporting numbers; Otsuka Pharmaceutical, which holds worldwide commercialization rights licensed in 2024, plans to discuss the data with the FDA and other global health authorities regarding potential expedited regulatory submission pathways. Separately, the IMAgINATION study of sefaxersen in adults with primary immunoglobulin A nephropathy, conducted by Ionis' partner Roche, met its primary endpoint in a prespecified interim analysis, showing statistically significant and clinically meaningful reductions in proteinuria after 37 weeks, and will continue in a blinded manner to evaluate kidney function over two years with estimated glomerular filtration rate at week 105 as the longer-term measure. Roche licensed sefaxersen from Ionis in 2022 and is responsible for the phase III study and future global development, regulatory and commercialization activities, while Ionis is eligible for milestone payments and tiered royalties on net sales of both drugs. The two wins follow back-to-back cardiovascular setbacks for Ionis, including the phase III CARDIO-TTRansform failure of Wainua with AstraZeneca in July and the phase III Lp(a)HORIZON miss for pelacarsen with Novartis, and come after the FDA approval of Zanvastro for Alexander disease earlier this month. Year to date, Ionis shares have lost 42% compared with the industry's 2% decline.

Roche announced positive prespecified interim results from the ongoing phase III IMAgINATION study of investigational sefaxersen in adults with primary IgA nephropathy, with the study meeting its primary endpoint of statistically significant and clinically meaningful proteinuria reduction versus placebo at 37 weeks as measured by 24-hour urine protein-to-creatinine ratio. Sefaxersen is a once-monthly subcutaneous injection designed for self-administration that inhibits complement factor B production in the liver, and its safety and tolerability profile was consistent with previously reported data with no new safety signals. The IMAgINATION study enrolled 459 people randomized 1:1 to receive sefaxersen or placebo for 105 weeks and will continue blinded to evaluate change in kidney function over two years as measured by estimated glomerular filtration rate at week 105. Interim data will be presented at an upcoming medical congress and shared with health authorities. Roche licensed sefaxersen from Ionis for the treatment of complement mediated diseases.

AbbVie reported second-quarter revenues of $16.99 billion, up 10.2% year on year and 1.2% above analysts' consensus expectations, though the quarter was mixed with only a narrow beat of EPS estimates and a slight miss of full-year EPS guidance estimates. The results came as the 11 therapeutics stocks tracked by the report collectively beat consensus revenue estimates by 8% in Q2, with share prices up 24.8% on average since the latest earnings results. Biogen posted the group's best quarter, with revenues of $2.74 billion, up 3.4% year on year and 12.1% above expectations, while Myriad Genetics delivered the weakest performance, reporting revenues of $190.7 million, down 10.5% year on year and 8.2% below expectations, alongside full-year revenue guidance that missed and a significant EPS miss. Gilead Sciences reported revenues of $7.80 billion, up 10.2% year on year and 6.2% above expectations, and Moderna reported revenues of $145 million, up 2.1% year on year and 35.8% above expectations, the biggest analyst estimate beat of the group. AbbVie's stock is up 2.9% since reporting and currently trades at $264.79.

Moderna will present detailed data from the phase III INTerpath-001 study of intismeran autogene, its personalized mRNA cancer therapy developed with Merck, at the European Society for Medical Oncology Congress next month. The findings will be presented on Oct. 24 in a Presidential Symposium, a session highlighting cutting-edge and potentially practice-changing clinical research, and are expected to provide investors with detailed data beyond the top-line results Moderna reported last month. Last month, Moderna and Merck reported positive results from INTerpath-001, which evaluated intismeran in combination with Merck's Keytruda in patients with high-risk Stage IIB-IV melanoma whose tumors had been surgically removed; the study met its primary endpoint of recurrence-free survival and a key secondary endpoint of distant metastasis-free survival, though the companies did not report numerical data, stating only that the improvements were statistically significant and clinically meaningful. The companies are advancing intismeran across nine phase II and phase III studies spanning multiple tumor types, including non-small cell lung cancer, bladder cancer and renal cell carcinoma, and a commercial launch of the therapy is targeted as early as next year. Moderna shares rose 12% yesterday, climbing to a new 52-week high of $176.86, and have skyrocketed nearly 500% year-to-date, significantly outperforming the industry's 6% growth.

ADARx Pharmaceuticals said on Monday it is targeting a valuation of up to $1.74 billion in its US initial public offering, joining a wave of biotech companies planning listings. The San Diego-based developer of RNA-based drugs for rare diseases aims to raise up to $371.9 million by offering 21.9 million shares priced between $15 and $17. AbbVie has agreed to invest up to $100 million in a concurrent private placement that would give it a roughly 4.9% stake post-IPO, adding to the $335 million it paid ADARx in May 2025 for a research collaboration. ADARx's most advanced candidate, onvuzosiran, is in late-stage testing for hereditary angioedema, a rare genetic disorder that causes sudden swelling attacks, and three of its programs are in clinical testing while two are in advanced preclinical development. JPMorgan, Morgan Stanley and TD Cowen are among the underwriters, and the shares will list on the Nasdaq under the symbol ADRX.