Tag: Anxiety

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There is no nature anymore

When people talk about “nature,” they’re generally talking about things that aren’t made by human beings. Rocks. Reefs. Red wolves. But while there is plenty of God’s creation to go around, it is hard to think of anything on Earth that human hands haven’t affected.

Mat Honan

In the Brazilian rainforest, scientists have found microplastics in the bellies of animals ranging from red howler monkeys to manatees. In remotest Yakutia, where much of the earth remains untrodden by human feet, the carbon in the sky above melts the permafrost below. In the Arctic Ocean, artificial light from ship traffic—on the rise as the polar ice cap melts away—now disrupts the nightly journey of zooplankton to the ocean surface, one of the largest animal migrations on the planet. The remote mountain lakes of the Alps are contaminated with all kinds of synthetic chemicals. Polar bears are full of flame retardants. Cesium-137, fallout from nuclear bomb explosions, lightly rimes the entire planet. 

These examples are mostly pollution—nuclear, carbon, chemical, light—but I raise them not to highlight the ways human industry and technology degrade the environment but to note how the things humans build change it. Nobody really knows what the exact effects of all that will be, but my point is that no part of the globe is free of human fingerprints. We have literally changed the world.  

We’ve changed ourselves as well. Humans are especially adept at bending human nature. Everything about us is up for grabs—appearance, health, our very thoughts. Pharmaceuticals, surgeries, vaccines, and hormones give us longer lives, take away our pain, ease our anxiety and depression, make us faster, stronger, more resilient. We’re getting glimpses of technologies that will let us change who our children will become before they’re even born. Electrodes implanted in people’s brains let them control computers and translate thoughts into speech. Prosthetics and exoskeletons straight out of comic books restore and enhance physical abilities, while gene-­editing technologies like CRISPR are rewriting our very DNA. And meanwhile, people have taken the sum total of all the information we have ever written down and poured it into vast calculating machines in an effort—at least by some—to build an intelligence greater than our own. 

So what even is nature, or natural, in this context? Is it “environmentalist,” in the conventional sense, to try to preserve what one could argue no longer exists? Should we employ technology to try to make the world more “natural”?  

Those questions led us to approach this Nature issue with humility. We try to grapple with them all the time—MIT Technology Review is, after all, a review of how people have altered and built upon nature.

And it’s a place to think about how we might repair it. Take solar geoengineering, for example—a subject we have covered with increasing frequency over the past few years. The basic idea of geoengineering is to find a technological fix for a problem technology caused: Burning ­petrochemicals to fuel the Industrial Revolution turned Earth’s atmosphere into a heat sink, fundamentally breaking the climate. Some geoengineers think that releasing particulate matter into the stratosphere would reflect sunlight back into space, thus reducing global temperatures. After years of theoretical discussions, some companies have begun to actively experiment with such technologies. This might seem like a great way to restore the world to a more natural state. It’s also fraught with controversy and peril. It could, for example, benefit some nations while harming others. It may give us license to continue burning fossil fuels and releasing greenhouse gases. The list goes on. 

Nature isn’t easy. 

In our May/June issue, we have attempted to take a hard look at nature in our unnatural world. We have stories about birds that can’t sing, wolves that aren’t wolves, and grass that isn’t grass. We look for the meaning of life under Arctic ice and within ourselves—and in the far future, on a distant world, courtesy of new fiction by the renowned author Jeff VanderMeer. I don’t know if any of that will answer the questions I’ve been asking here—but we can’t help but try. It’s in our nature. 

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Number of children and maternal mental health in the context of China’s fertility policy transition: the moderating effect of employment status and the mediating effect of family environment

BackgroundHaving more children may be detrimental to maternal mental health during China’s ongoing fertility policy transition. However, under what circumstances and how number of children could be associated with maternal mental health remains understudied in China. This study examined the association between number of children and maternal anxiety and depressive symptoms among mothers of middle school students in Shanghai, China. It also explored the moderating effect of maternal employment status and the mediating effect of family environment.MethodsMothers of students from 7 middle schools in Shanghai were surveyed. In total, 4,215 valid questionnaires were obtained. The survey included sociodemographic information, the Generalized Anxiety Disorder Scale (GAD-7), the Center for Epidemiologic Studies Depression Scale (CES-D), and the Chinese version of the Family Environment Scale (FES-CV). Multiple linear regression analysis was performed to examine the association between number of children and maternal anxiety/depressive symptoms. Model 1 and Model 4 of SPSS PROCESS were then employed to examine the moderating effect of employment status and the mediating effect of family environment.ResultsThe rates of clinically significant anxiety and depressive symptoms among mothers were 13.6% and 17.6%, respectively. The moderating effect of maternal employment status was significant. Among unemployed mothers, number of children was positively associated with both maternal anxiety and depressive symptoms, whereas among employed mothers, number of children was not associated with maternal anxiety or depression. Among unemployed mothers, family environment mediated the association between number of children and maternal anxiety/depressive symptoms through the pathways of family conflict and organization. Among employed mothers, family environment suppressed the association between number of children and maternal anxiety/depressive symptoms through the pathways of family conflict, intellectual-cultural orientation, organization, control, and independence.ConclusionOur findings suggest that number of children per se is not necessarily associated with worsened maternal mental health. Instead, the potential changes in employment participation and family environment that accompany having more children may be more relevant. Therefore, stakeholders, clinicians, and researchers should therefore focus on these aspects when addressing maternal mental health.
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Effect of a nursing-based information–motivation–behavioral model on older patients with type 2 diabetes mellitus

BackgroundOlder patients with type 2 diabetes mellitus (T2DM) frequently encounter challenges, including a diminished capacity for self-management, a high prevalence of negative emotions, and cognitive decline and physiological changes attributable to long-term disease burden, leading to compromised glycemic control and impaired quality of life. Traditional diabetes nursing interventions often lack systematic strategies to address the psychological and cognitive needs specific to this patient population. The Information-Motivation-Behavioral Skills (IMB) model is a theoretical framework designed to promote health behavioral changes; however, research investigating its specific application in regulating psychological state and managing cognitive function in older patients with T2DM remains limited.AimTo investigate the effectiveness of a nursing intervention based on the IMB model in older patients with T2DM.MethodsData from 86 older patients with T2DM were divided into 2 groups: intervention (structured IMB model-based nursing + routine care [n = 43]); and control (conventional T2DM care [n = 43]). Psychological state (Self-Rating Anxiety and Depression Scales [SAS, SDS]), cognitive function (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]), glycemic control (fasting blood glucose [FBG], 2 h postprandial blood glucose [2hPBG], and glycated hemoglobin A1c [HbA1c]), and satisfaction with nursing were compared between the 2 groups before and after a three-month intervention.ResultsSAS and SDS scores significantly decreased in both groups after intervention, with a more pronounced reduction in the intervention group (P < 0.05). MMSE and MoCA scores improved in both groups, with significantly higher scores in the intervention group (P < 0.05). Glycemic control (FBG, 2hPBG, and HbA1c) improved substantially in the intervention group (P < 0.05). Satisfaction with nursing among the intervention group (95.35%) was significantly greater than that in the control group (79.07%) (P < 0.05).ConclusionThe IMB model-based nursing intervention alleviates anxiety and depression, improves cognitive function, enhances glycemic control, and increases satisfaction with nursing in older patients with T2DM, thus meriting broader clinical implementation.
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Coping under pressure: police-specific stressors and mental health in Catalonia police forces

IntroductionPolice officers are exposed to elevated psychological risks due to both operational and organizational stressors. Additionally, police officers tend to resort to avoidant coping strategies, which exacerbate poor mental health outcomes, such as burnout and PTSD.MethodsThis study aims to examine clinical symptoms (stress, anxiety, depression), coping styles, and perceived stressors among police forces from Catalonia, Spain. A total of 741 officers completed an online survey comprising DASS-21, PSQ-Op, PSQ-Org, Brief COPE and brief open-ended questions. ResultsOverall, both operational and organizational stressors were significant predictors of clinical symptoms, with the latter revealing a more pronounced impact. Avoidant coping emerged as the strongest risk factor for distress, while problem-focused coping emerged as a possible protective factor, especially against depression. Both gender and years of service influenced coping strategies: i) female officers reported higher use of adaptive coping, while male officers scored higher in avoidant coping; and ii) more experienced officers reported lower anxiety symptoms but also lower use of active coping strategies. DiscussionThese findings underscore the importance of addressing both organizational culture and individual-level factors in promoting psychological resilience, while considering gender and career stage to support sustainable mental health within police forces.
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Popular Online Content as a Treatment-as-Usual Control in Digital Mental Health Intervention Trials: Secondary Analysis of Two Online Randomized Controlled Trials With Repeated Measures

Background: Treatment-as-usual (TAU) conditions are intended to reflect the support typically received in routine treatment settings. For digital mental health interventions (DMHIs) delivered online, TAU conditions should reflect the usual patterns of online help-seeking. The lack of ecologically valid TAU control conditions has been a gap in effectiveness trials of online DMHIs. In this study, mental health–related popular online content (eg, advice TikToks, lived experience vlogs, and self-care infographics) was examined as a valuable TAU control condition. Objective: This study examined the feasibility of popular online content as a TAU control condition in DMHI trials. Methods: This study was a secondary analysis of two randomized controlled trials. Both trials recruited participants online, primarily via an online study recruitment platform. In study 1 (N=916), US adults with elevated depression or anxiety were randomized to either (1) complete a single-session DHMI for depression and anxiety (n=291), (2) search the web for popular online content relevant to their struggles (n=312), or (3) search a curated library of mental health–related popular online content (n=313). In study 2 (N=431), US adults with elevated loneliness were randomized to (1) complete a single-session DHMI for loneliness (n=136), (2) search a curated library of popular online content related to loneliness (n=145), or (3) complete an attention-matched control condition (n=150). All 6 programs took approximately 10 to 20 minutes to complete and were entirely self-guided. Participants rated each program’s credibility and expected benefit, as well as their feelings of distress (study 1) and loneliness (study 2). The studies did not involve interaction between participants and the research team. Results: In study 1, dropout during the treatment was 4.8% (14/291) for the single-session intervention, 25.9% (81/312) for online help-seeking, and 9.6% (30/313) for the curated library. The curated library’s credibility and expected benefit score did not differ from that of the single-session intervention (Cohen =0.08; =.88) and was higher than that of unguided help-seeking (Cohen =0.23; =.01). In study 2, dropout was higher in the curated library condition (7/145, 4.8%) than in the single-session intervention and the attention-matched control condition (0/136, 0.0% and 0/150, 0.0%). The mean credibility and expected benefit score for the curated library was comparable to that of the attention-matched control condition (Cohen =0.00; >.99) but lower than that of the single-session intervention (Cohen =0.32; =.02). Changes in distress and loneliness from baseline to 8-week follow-up did not differ across the conditions in study 1. All effect sizes were small in study 1 (Cohen <0.15 and no comparisons were statistically significant >.06). Similarly, in study 2, all effect sizes were small (Cohen <0.12), and no comparisons were statistically significant (>.25). Conclusions: Curated libraries of popular online content are a feasible, ecologically valid TAU benchmark for effectiveness trials of online DMHIs. Future research on TAU conditions in online help-seeking contexts should better align with observed DMHI attrition rates and account for the increasingly central role of conversational artificial intelligence in online mental health support. Trial Registration: OSF Registries 3DYMA; https://osf.io/3dyma and NVD79; https://osf.io/nvd79; ClinicalTrials.gov NCT05687162; https://clinicaltrials.gov/study/NCT05687162
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Altered static and dynamic regional homogeneity in basal ganglia–thalamocortical circuits and their association with neuropsychiatric manifestations in Wilson’s disease

PurposeWilson’s disease (WD) is an autosomal recessive disorder caused by ATP7B mutations, resulting in impaired copper metabolism and progressive neuropsychiatric manifestations. This study investigated spatiotemporal alterations in regional brain activity using static and dynamic resting-state fMRI with regional homogeneity (ReHo), and their relationships with clinical features.MethodsResting-state fMRI data were acquired from WD patients and healthy controls (HCs). Static and dynamic ReHo analyses were performed to characterize local synchronization strength and temporal variability of spontaneous neural activity. Group differences were assessed across the basal ganglia, thalamus, cerebellum, and cortical regions. Associations between altered ReHo metrics and clinical measures were evaluated with FDR correction for multiple comparisons.ResultsCompared with HCs, WD patients exhibited widespread ReHo abnormalities involving the basal ganglia (putamen and globus pallidus), thalamus, cerebellum, and cortical regions. Static ReHo in the left putamen and globus pallidus was positively associated with anxiety severity, while right putaminal ReHo was negatively associated with neurological severity and positively associated with disease duration. Dynamic ReHo in the left middle frontal gyrus showed negative associations with depression severity and disease duration. All brain–behavior correlations survived FDR correction, indicating robust effects.ConclusionWD is characterized by disrupted spatiotemporal organization of local functional synchronization within cerebellar and basal ganglia–thalamo–cortical circuits. These findings support a network-level dysfunction model involving subcortical synchronization deficits and cortical temporal instability, which together underpin neuropsychiatric manifestations and disease progression.
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Twelve-month outcomes and comparative costs of internet-delivered psychodynamic therapy versus cognitive-behavioral therapy for adolescent depression: a randomized controlled trial

IntroductionAdolescent depression poses a major public health concern with substantial clinical and societal implications. Both internet-delivered cognitive behavioural therapy (ICBT) and internet-delivered psychodynamic therapy (IPDT) have shown efficacy, but questions remain regarding long-term efficacy and cost-effectiveness. The present study presents a 12-month follow-up and cost-comparison from a randomized controlled trial (RCT) comparing ICBT and IPDT for adolescent depression.MethodsParticipants were 272 adolescents aged 15–19 with a primary diagnosis of major depressive disorder. The primary outcome was depressive symptoms measured with the QIDS-A17-SR while the secondary outcome was anxiety symptoms measured with the GAD-7. Costs were assessed both by comparing costs of treatment and healthcare use 12-month post-treatment using the TIC-P.ResultsResults were stable at the 12-month follow up compared to treatment endpoint, for both depressive and anxiety symptoms. There were no significant group differences at the 12-month follow-up. There were no differences in treatment costs or in costs for healthcare use one-year post-treatment.DiscussionThis study suggests that treatment gains from IPDT and ICBT for adolescent depression remain stable during a 12-month follow-up period, with no differences between the treatments one-year post-treatment. Furthermore, it suggests comparable costs for the treatments. Interpretation of health-care use data was restricted due to the COVID-19 pandemic taking place during the follow-up period. This adds to the literature suggesting that ICBT and IPDT can be seen as viable alternatives for treating adolescent depression. More research into the long-term effects and cost-effectiveness is needed.
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StockWatch: Revolution’s Phase III Pancreatic Cancer Data Dazzles Investors, Analysts

Pancreatic cancer is one of the most difficult cancers to treat, with an overall five-year survival rate of 13%, according to the American Cancer Society, stretching from 3% for metastatic (Stage 4) to 44% for localized (Stages 1 and 2).

Dismal odds such as these explain the enthusiastic response of investors when Revolution Medicine (NASDAQ: RVMD), a developer of RAS-addicted cancer therapies, announced dazzling data from its Phase III RASolute 302 trial (NCT06625320) evaluating its once-daily oral daraxonrasib in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who had been previously treated.

In the trial’s overall (intent-to-treat) study population, daraxonrasib showed a median overall survival (OS) of 13.2 months, nearly double the 6.7 months demonstrated for standard-of-care chemotherapy, with a hazard ratio (HR) of 0.40 (p < 0.0001). Daraxonrasib also presented what Revolution called a manageable safety profile and no new safety signals.

“These results represent a potentially transformative advance for patients and underscore daraxonrasib’s potential to redefine the treatment landscape. We are moving with urgency toward global regulatory submissions and remain committed to rapidly advancing this therapy for patients with a broad range of RAS-addicted cancers, Revolution’s CEO and chairman Mark A. Goldsmith, MD, PhD, said in a statement.

Investors and analysts largely agreed with Goldsmith. Revolution’s stock reacted to the data release by soaring 54% this past week, starting with a 41% surge that sent the share price soaring from $96.43 on April 10 to $136.30 on April 13. Since then, the stock has jumped another 12%, reaching $152.54 at Wednesday’s closing bell. Profit-taking by investors led to a 2% slide on Thursday (to $149.27) and a 0.43% dip on Friday (to $148.63).

“Our base case from stats sim [statistics simulation] was 11 vs. 7 mos, and based on our investor discussions, OS >12 months (and/or >6 mos delta vs. chemo) should drive meaningful stock upside,” Faisal Khurshid, an equity analyst with Jefferies, correctly predicted in an April 13 research note.

A “clear win” scenario, Khurshid explained, would show daraxonrasib with an OS of greater than 11 to 12 months, and/or a daraxonrasib difference vs. chemo of >4–6 months, and/or an HR of <0.5–0.6.

“Best-case outcome”

“The disclosed data materially exceeds these expectations,” Khurshid declared. “This is by any measure a best-case outcome for RVMD [emphasis in original]. Darax’s performance was roughly in line with the Ph1 experience, and chemo only slightly outperformed historical benchmarks.”

Revolution’s positive data sets the bar high for other cancer treatment developers—including Erasca (NASDAQ: ERAS), which is expected by the end of the first half to announce initial monotherapy data from its Phase I trial (NCT06983743) assessing ERAS-0015, a RAS-targeting molecule, in patients with RAS-mutant solid tumors.

Khurshid’s colleague at Jefferies, Maury Raycroft, PhD, noted Erasca has said it believes a >10% improvement in response rates in PDAC or non-small cell lung cancer compared to daraxonrasib could support ERAS-0015 as being differentiated from Revolution’s candidate, as would improvement in two or more safety/tolerability attributes, such as rash, gastrointestinal diseases, and stomatitis.

“Given the efficacy seen in ERAS’ 8 mg cohort and escalation to 40 mg, we remain (+)ve on the pot’l for stronger activity at higher doses,” Raycroft wrote in an April 13 research note. “That said, improved safety may be a key differentiator, particularly to enable combinations, especially as the competitive benchmark in PDAC continues to move higher.”

At Leerink Partners, Jonathan Chang, PhD, senior managing director, emerging oncology, and a senior research analyst, raised the firm’s 12-month share price target 28%, from $115 to $147, “to reflect greater conviction in pipeline opportunities.”

“Although RAS pathway drug development is highly competitive, we continue to believe encouraging clinical data from the innovative RAS(ON) platform, coupled with the large addressable population of RAS-dependent cancers, support a positive long-term outlook for RVMD,” Chang wrote.

Leerink colleague Andrew Berens, MD, senior managing director, targeted oncology, and a senior research analyst, observed that daraxonrasib could set a standard for positive data that several RAS-based cancer drug developers are working to improve upon, citing:

  • Adlai Nortye (NASDAQ: ANL): Its panRAS inhibitor AN9025 shares the same method of action as daraxonrasib but with potentially greater potency and durability. The company’s pipeline also includes AN4035, a panRAS antibody-drug conjugate.
  • BridgeBio Oncology Therapeutics (NASDAQ: BBOT): Its BBO-11818, a pan KRAS ON/OFF inhibitor, has shown efficacy signals in early PDAC clinical studies. “The more targeted ON/OFF approach may lead to greater potency and less toxicity.”
  • Immuneering (NASDAQ: IMRX): Its atebimetinib showed 64% OS at 12 months as a first-line pancreatic cancer treatment in updated data announced January 7.

“Not insurmountable”

“Dara[xonrasib] sets a high bar that is not insurmountable. The data for dara look encouraging, with a clear benefit over SOC [standard-of-care] chemo, but could leave room for other novel approaches to improve on efficacy and/or tolerability,” Berens wrote. “We think dara could be the first targeted therapy for RAS mutant PDAC patients and potentially become the 2L SOC, establishing RAS inhibitors as key backbone therapies in PDAC.”

That could lead to more RAS-based combination therapies, which Berens said has favorable implications for Tango Therapeutics (NASDAQ: TNGX)’s vopimetostat, an oral, selective PRMT5 inhibitor being studied in combinations with either daraxonrasib and another Revolution RAS(ON) cancer candidate, zoldonrasib, in a Phase I/II trial (NCT05732831).

Revolution said it plans to present its data at the American Society of Clinical Oncology’s 2026 ASCO Annual Meeting, set for May 29–June 2 in Chicago. Data will also be presented to regulators as Revolution files a New Drug Application (NDA) with the FDA, which has selected daraxonrasib for its Commissioner’s National Priority Voucher (CNPV).

Launched in October by FDA Commissioner Martin A. Makary, MD, CNPV is a pilot program that awards vouchers to drug developers whose work is deemed to address a health crisis in the United States, deliver more innovative cures, address unmet public health needs, and increase domestic drug manufacturing as a national security issue. In return, the vouchers entitle companies to reviews of their final applications within a target timeframe of 1–2 months rather than the current 10–12 months.

The stock surge boosted Revolution’s market capitalization (share price times the number of outstanding shares) to approximately $30 billion. That’s the midpoint of the $28 billion to $32 billion acquisition that Merck & Co. (NYSE: MRK) was pursuing for Revolution in January, according to the Financial Times. That prospective deal reportedly collapsed after the companies failed to agree on the value of daraxonrasib and Revolution’s other cancer-fighting candidates.

Merck never commented on its pursuit of Revolution, while AbbVie (NYSE: ABBV) flatly denied an earlier report that it sought to acquire the cancer drug developer. All the acquisition talk surrounding Revolution landed the company on GEN’s updated A-List Top 10 Takeover Targets of 2026, published March 9.

Cashing in

Revolution quickly cashed in on its positive data and stock surge, first proposing a $1 billion public offering of stock and debt, then doubling the size to $2 billion. The $2 billion offering consisted of concurrent public offerings of 10,563,381 shares of common stock at $142 per share (approximately $1.5 billion in gross proceeds) and $500 million of 0.50% convertible senior notes due 2033. Revolution also granted underwriters of the common stock offering a 30-day option to purchase up to an additional 1,584,506 shares.

J.P. Morgan, TD Cowen, and Guggenheim Securities are book-running managers for the stock and note offering, with LifeSci Capital acting as lead manager.

Daraxonrasib (formerly RMC-6236) is an oral RAS(ON) multi-selective, non-covalent inhibitor designed to target cancers driven by a variety of common RAS mutations, including PDAC, non-small cell lung cancer (NSCLC), and colorectal cancer. It is now under study in four global Phase III registrational trials—three in PDAC, the other in NSCLC. Daraxonrasib has been granted the FDA’s Breakthrough Therapy and Orphan Drug designations for the treatment of patients with previously treated metastatic PDAC harboring G12 mutations.

The RASolute 302 trial is a 501-patient global, randomized, registrational clinical study designed to evaluate the efficacy and safety of daraxonrasib as a monotherapy in patients with previously treated metastatic PDAC. Patients were randomized to receive either an oral dose of 300 mg daraxonrasib once daily or investigator’s choice of standard of care cytotoxic chemotherapy. The trial enrolled patients with metastatic PDAC harboring a wide range of RAS variants, including those with RAS G12 mutations (such as G12D, G12V, and G12R), as well as patients without an identified tumor RAS mutation (wild type).

Primary endpoints of RASolute 302 are OS and progression-free survival (PFS), as well as OS in patients with tumors harboring RAS G12 mutations. Secondary endpoints include PFS and OS in all enrolled patients (the intent-to-treat population) encompassing patients with and without identified tumor RAS mutations, as well as objective response rate, duration of response, and patient-reported quality of life.

Kailera makes history with $625M IPO

The “sign of life” StockWatch reported on last week when Avalyn Pharma filed paperwork for an initial public offering (IPO) is blooming this spring into a full blown comeback for IPOs, paced by what market watchers called the largest-ever public offering for a U.S. biotech—the eye-popping $625 million IPO carried out by Kailera Therapeutics—with at least two other companies submitting paperwork for filings of their own.

Kailera is a developer of therapies for obesity and weight management based on glucagon-like peptide receptor 1 (GLP-1) agonists, alone or in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. The company priced an IPO on Thursday that generated $489.7 million in net proceeds through the sale of 39,062,500 shares of common stock at $16 per share—the high end of the pricing range of $14–$16.

On Kailera’s first full day of trading on Friday, investors showered the company with buys, propelling a 72% leap that sent shares to a high of $27.50 before the stock settled for a 62.5% gain, closing at an even $26.

The company earlier anticipated $458.7 million in net proceeds based on a $15 per share IPO price—though any $1 increase to the IPO price would increase what Kailera netted from the offering by an additional $31 million, according to an amended Form S-1 registration statement filed April 13 with the U.S. Securities and Exchange Commission (SEC).

Net proceeds could ultimately be even higher, since Kailera has granted its underwriters a 30-day option to purchase up to an additional 5,859,375 shares at the IPO price minus underwriting discounts and commissions. J.P. Morgan, Jefferies, Leerink Partners, TD Cowen, and Evercore ISI are joint book-running managers for the offering, with William Blair acting as lead manager.

Pipeline development

Kailera said the IPO plus its cash, cash equivalents, and marketable securities would give the company resources that it intended to spend on developing its four clinical-phase pipeline candidates, all in-licensed for $100 million upfront from Jiangsu Hengrui Pharmaceuticals (Shanghai Stock Exchange: 600276):

  • Ribupatide, the company’s lead product and a once-weekly injectable GLP-1/GIP receptor dual agonist peptide, including to fund three ongoing global Phase III KaiNETIC clinical trials into the second quarter of 2028 (more than $625 million, the estimate based on the $15 share price)
  • Oral ribupatide, a once-daily oral tablet formulation of ribupatide, including the funding of planned Phase III trials into the second quarter of 2028 (more than $150 million)
  • KAI-7535, a once-daily oral small molecule GLP-1 receptor agonist, including through the completion of a planned Phase II clinical trial (more than $50 million)
  • Other R&D activities, including development of KAI-4729, a once-weekly injectable GLP-1/GIP/glucagon receptor tri-agonist, as well as for working capital and other general corporate purposes (Remaining proceeds, not quantified)

Kailera gained exclusive global rights outside Greater China to Jiangsu Hengrui’s GLP-1 portfolio in 2024. That year, Kailera was launched with a $400 million Series A financing co-led by Atlas Venture, Bain Capital Life Sciences, and RTW Investments. Last October, Kailera garnered an additional $600 million in Series B financing led by a new investor, Bain Capital Private Equity.

“Our obesity-first approach seeks to capitalize on and improve upon proven science to advance product candidates which have the potential to maximize weight loss and address other critical needs in the current therapeutic landscape and to provide options, including oral options and alternative mechanisms, for people living with obesity no matter where they are in their treatment journey,” Kailera stated in its amended registration statement.

Kailera has adjusted the value of its cash and equivalents plus marketable securities from $652.728 million to a pro forma $1.142 billion in assets, reflecting the conversion of all outstanding preferred shares into common stock upon closing of the offering, plus an amended and restated certificate of incorporation.

Kailera’s IPO has surpassed the previous record-high among U.S. biotechs, the $604 million offering of Moderna (NASDAQ: MRNA) in December 2018, two years before the messenger RNA (mRNA) vaccine developer won FDA emergency authorization for its COVID-19 vaccine.

In the works

At least two other biotechs have filed Form S-1 registration statements for future IPOs in recent days, without disclosing how many shares they plan to raise or their offering prices.

  • Seaport Therapeutics is a developer of treatments for depression, anxiety, and other debilitating neuropsychiatric disorders based on its GlyphTM platform, a lymphatic-targeting prodrug technology designed to enhance a drug’s oral bioavailability and reduce side effects by bypassing first-pass metabolism. “Through our differentiated approach, we identify clinically validated mechanisms with established efficacy and safety profiles that have historically been limited by high first-pass metabolism, low bioavailability, and/or side effects,” Seaport stated in its Form S-1
  • Hemab Therapeutics, a developer of subcutaneous treatments for rare blood coagulation disorders, said its lead candidate, sutacimig (HMB-001), is a bispecific antibody in Phase I/II trials for the prophylactic treatment of Glanzmann thrombasthenia and Phase II studies for the prophylactic treatment of Factor VII deficiency. Another therapeutic candidate, HMB-002, is a monovalent antibody in Phase I/II trials for the subcutaneous prophylactic treatment of Von Willebrand disease. “We are building a franchise designed to address select coagulation disorders where we believe advances in biology, drug modality, and care delivery have the potential to meaningfully improve disease management,” Hemab stated in its Form S-1.

Leaders and laggards

  • MeiraGTx (NASDAQ: MGTX) shares yo-yoed, rising 26% from $8.97 to $11.29 Tuesday, after the company announced plans to present three-year data from its Phase I AQUAx trial (NCT04043104) evaluating AAV-hAQP1 in Grade 2/3 radiation-induced xerostomia. MeiraGTx reported “clinically meaningful” improvements in xerostomia symptoms, such as the average XQ score improving by 17 points (39.5%) at month 12, bilaterally treated participants reporting greater improvement than those treated unilaterally (21 points vs 13 points), and 75% of bilaterally-treated patients reporting transformative (≥10 point) improvement at month 12. After dipping 0.4% to $11.25 Wednesday, shares slumped 16% to $9.48 Thursday as MeiraGTx priced an approximately $100 million offering of 11,111,111 shares at $9 per share. Proceeds plus existing cash and cash equivalents are expected to fund commercial launches of AAV-hAQP1 and botaretigene sparoparvovec (“bota-vec”), a gene therapy for XLRP that MeiraGTx agreed to acquire from Johnson & Johnson (NYSE: JNJ) for $25 million cash upfront, a $50 million one-time payment tied to achieving specified regulatory and commercial milestones, plus a “mid-teens” royalty on global net sales starting on or after July 1, 2029.
  • Travere Therapeutics (NASDAQ: TVTX) shares soared 37% from $30.70 to $42.13 Tuesday after the rare disease drug developer won full FDA approval for Filspari® (sparsentan) in a second rare kidney disease. Filspari has become the first and only treatment for focal segmental glomerulosclerosis (FSGS), specifically to reduce proteinuria in adults and younger patients ages eight years and older with FSGS without nephrotic syndrome. Filspari won FSGS approval based on positive data from the Phase III DUPLEX trial (NCT03493685), where researchers reported a statistically significant 46% reduction in proteinuria from baseline to Week 108 in patients treated with Filspari vs. 30% for those treated with standard of care maximum labeled dose irbesartan, marketed by Sanofi (Euronext Paris: SAN) as Avapro®. Filspari first won FDA approval in 2023 to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression.

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