Radically different
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.
“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:
“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.
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.
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.
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):
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.
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.
The post StockWatch: Revolution’s Phase III Pancreatic Cancer Data Dazzles Investors, Analysts appeared first on GEN – Genetic Engineering and Biotechnology News.
The handsome new book Maintenance: Of Everything, Part One, by the tech industry legend Stewart Brand, promises to be the first in a series offering “a comprehensive overview of the civilizational importance of maintenance.” One of Brand’s several biographers described him as a mainstay of both counterculture and cyberculture, and with Maintenance, Brand wants us to understand that the upkeep and repair of tools and systems has profound impact on daily life. As he puts it, “Taking responsibility for maintaining something—whether a motorcycle, a monument, or our planet—can be a radical act.”
Radical how? This volume doesn’t say. In an outline for the overall work, Brand says his goal is to “end with the nature of maintainers and the honor owed them.”
The idea that maintainers are owed anything, much less honor, might surprise some readers. Actually, maintenance and repair have been hot topics in academia since the mid-2010s. I played some role in that movement as a cofounder of the Maintainers, a global, interdisciplinary network dedicated to the study of maintenance, repair, care, and all the work that goes into keeping the world going.
Brand is right, too, that maintainers haven’t gotten the laurels they deserve. Over the past few decades, scholars have shown that work from oiling tools to replacing worn parts to updating code bases all tends to be lower in status than “innovation.” Maintenance gets neglected in many organizational and social settings. (Just look at some American infrastructure!) And as the right-to-repair movement has shown, companies in pursuit of greater profits have frequently locked us out of being able to do repairs or greatly reduced the maintainable life of their products. It’s hard to think of any other reason to put a computer in the door of a refrigerator.
Some of Brand’s earlier work helped inspire those insights. But his new book makes me think he doesn’t see things that way. For Brand, maintenance seems to be a solitary act, profound but more about personal success and fulfillment than tending to a shared world or making it better.
Born in 1938, Brand is 87 years old. A sense hangs over the book—with its battles against corrosion, rust, and decay, with its attempts to keep things going even as they inevitably falter—of someone looking over life and pondering its end. Maintenance: Of Everything connects to every stage of Brand’s life. It’s worth reviewing where it falls in that arc. Brand has always been interested in tools and fixing things, but rarely has he focused on the systems that need the most care.
More than a half-century ago, Brand was a member of the Merry Pranksters, a countercultural, LSD-centered hippie collective famously led by Ken Kesey, the author of One Flew Over the Cuckoo’s Nest. In 1966, Brand co-produced the Trips Festival, where bands like the Grateful Dead and Big Brother and the Holding Company performed for thousands amid psychedelic light shows.
Brand’s Whole Earth Catalog had a vision that might feel progressive, but its libertarian, rugged-individualist philosophy of remaking civilization alone stood in contrast to more collective social change movements.
In some ways, the Trips Festival set a paradigm for the rest of his life’s work. Brand’s biographers have described him as a network celebrity—someone who got ahead by bringing people together, building coalitions of influential figures who could boost his signal. As Kesey put it in 1980, “Stewart recognizes power. And cleaves to it.”
Brand applied this network logic to the undertaking he will always be best remembered for: the Whole Earth Catalog. First published in 1968 and aimed at hippies and members of the nascent back-to-the-land movement, the publication had the motto “Access to tools.” Its pages were full of Quonset huts, geodesic domes, solar panels, well pumps, water filters, and other technologies for life off the grid. It was a vision that might feel progressive or left-leaning, but the libertarian, rugged-individualist philosophy of eschewing corrupt systems and remaking civilization alone stood in contrast to the more collective movements pushing for deep social change at the time—like civil rights, feminism, and environmentalism.
That vision also led straight to the empowerment that came with new digital tools, and to Silicon Valley. In 1985, Brand published the Whole Earth Software Catalog, the last of the series, and also cofounded the WELL—the Whole Earth ’Lectronic Link, a pioneering online community famous for, among other things, facilitating the trade of Grateful Dead bootlegs. He also wrote a hagiographic book about the MIT Media Lab, known for its corporate-sponsored research into new communications tech. “The Lab would cure the pathologies of technology not with economics or politics but with technology,” Brand wrote. Again, not collective action, not policymaking: tools. And Brand then cofounded the Global Business Network, a group of pricey consulting futurists that further connected him to MIT, Stanford, and the Valley. Brand had literally helped bring about the modern digital revolution.
His attention then turned toward its upkeep. Brand’s 1994 book, How Buildings Learn: What Happens After They’re Built, argued against high-modernist architectural ideas. Nearly all buildings eventually get remade, he argued, but he especially favored cheap, simple structures that inhabitants could easily retool to suit changing needs. In some ways, Brand was recapitulating the liberated—or libertarian—philosophy of the Whole Earth Catalog: People can remake their world, if they have access to tools. In a chapter titled “The Romance of Maintenance,” he asked readers to see the beauty, value, and occasional pleasures of fixer-uppers of all kinds.
This chapter was a touchstone for many of us in the academic subfield of maintenance studies. Researchers in disciplines like history, sociology, and anthropology, as well as artists and practitioners in fields like libraries, IT, and engineering, all started trying to understand the realities and, yes, romance of maintenance and repair. Brand joined and contributed to Listservs, attended conferences, chatted with intellectual leaders. So it’s a bit uncharitable when he writes that his new book is “the first to look at maintenance in general.” He knows better. The real question, though, is what his work has to teach us that others have not said before. In this first volume, the answer is unclear.
Maintenance: Of Everything, Part One is an odd book. If so much of Brand’s thinking has been about access to tools, he now asks, in a more extended way: How are our tools maintained? But where Brand began his career with a catalogue, in this volume we get … what? A digest? An almanac? An encyclopedia? Its form and riotous variety fit no genre easily.
The book has two chapters. The first, “The Maintenance Race,” recounts the story of three men who took part in the Golden Globe, a round-the-world race for solo sailors held in 1968. Each of the sailors, Brand explains, had a different philosophy of maintenance. One neglected it and hoped for the best. He died. Another thought of and prepared for everything in advance, and while he didn’t win the race, he completed it and once held the record for the “world’s longest recorded nonstop solo sailing voyage.” The final sailor won and did so through heroic acts of perseverance; his style was “Whatever comes, deal with it,” Brand explains. Structured like a fairy tale and unremittingly romantic, the story—like most of the anecdotes in the book—focuses on the derring-do of vigorous white guys. The strategy is no secret. Brand’s outline explains: “Start with a dramatic contest of maintenance styles under life-critical conditions—a true story told as a fable.” This myth is meant to inspire.
The second chapter, “Vehicles (and Weapons),” is over 150 pages long. It has five sections, multiple subsections, five subsections designated “digressions,” one called a “subdigression,” two “postscripts,” and several “footnotes” that are not footnotes in a formal sense but, rather, further addenda. At times, it all feels like notes for a future work. Brand makes no apology for the book’s woolliness. “All I can offer here,” he writes, “is to muse across a representative of maintenance domains and see what emerges.” Perhaps the most charitable reading of the potpourri is that it represents the return of a Merry Prankster, offering us a riotous varied light show. It’s a good book to leave on a table and occasionally open to a random page for entertainment. But it often seems as if it does not know what it wants to say or be.
“Vehicles (and Weapons)” begins by paraphrasing two famous works of maintenance philosophy, Robert M. Pirsig’s Zen and the Art of Motorcycle Maintenance and Matthew B. Crawford’s Shop Class as Soulcraft. Maintenance involves both “problem finding” and “problem solving.” While much repair work is marked by anxiety, impatience, and boredom, it also offers positive values and outcomes. “Motorcycle maintainers take heart from what they repair for—the glory of the ride,” Brand writes.
The beauty and triumph of cheapness is a running theme throughout the work, harking back to How Buildings Learn. Henry Ford’s Model T won out over early electric vehicles and hugely expensive luxury vehicles like Rolls-Royce’s Silver Ghost because it was cheap and easier to maintain. The three most popular cars in human history—the Ford Model T, the Volkswagen Bug, and the Lada “Classic” from Russia—all privileged cheapness, “retained their basic design for decades, and … invited repair by the owner.” Or, to be fair, maybe demanded it? For every hobbyist who delighted in being able to self-reliantly keep a VW running, there must have been thousands who appreciated how cheap it was and hated that it broke a lot. Brand never points to social research, like surveys, that might help us know people’s feelings on such matters.
Other sections recount how Americans created interchangeable parts (enabling not only cheap mass production but also easy maintenance), examine how maintenance works with assault rifles and in war, and track the history of technical manuals from the early modern period to the age of YouTube. These stories are solid, but they’re also well known to students of technology, and nearly all are recycled from the work of others, featuring many large block quotes. The volume breaks little new ground.
Brand treats maintenance as an unalloyed good. But the field of maintenance studies has moved on, burrowing into the domain’s ironies, complexities, and difficulties. A simple example: In most cases, it is environmentally far better to retire and recycle an internal-combustion vehicle and buy an electric one than to keep the polluting beast going forever. Maintaining a gas-guzzler or a coal-burning power plant isn’t a radical act but a regressive one. Also, maintenance can become a life-breaking burden on the poor, and it falls inequitably on the shoulders of women and people of color. Keeping existing systems going can be a way of avoiding tough, necessary change—like making technological systems more accessible for people with disabilities. In this volume, Brand is uninterested in such difficult trade-offs. He avoids any question of how politics shapes these issues, or how they shape politics.
This avoidance comes out most clearly in a section of “Vehicles (and Weapons)” that talks about Elon Musk—a character of “unique mastery,” Brand informs us. He tells us that Bill Gates once shorted Tesla’s stock, only to lose $1.5 billion. The lesson is clear: Elon won.
In what political and social vision is money the best way to keep the score? Brand rightly points out that electric vehicles have fewer moving parts and, in that sense, are more maintainable than internal-combustion vehicles. He celebrates Musk most of all because his products “have all proven to be game changers in part because they combine ingenious design with surprisingly low cost.” Again, it’s Brand’s “cheap, available tools” hypothesis. But there’s a real superficiality and lack of follow-through in thinking here: Teslas remain luxury vehicles whose sales have slumped since federal tax subsidies disappeared. The company has faced several right-to-repair lawsuits; there’s even a law review article on the topic. Musk is in no sense a maintenance hero. Yet Brand writes that with his companies, “Musk may have done more practical world saving than any other business leader of his time.” By the time Brand was writing this book, the controversies surrounding Musk for at least flirting with antisemitism, racism, sexism, authoritarianism, and more were quite clear. About this, the book says not a word.
For sure, Brand needn’t agree with Musk’s critics, but failing to even broach the subject is tone deaf and out of touch. Others have argued that Silicon Valley’s “Move fast and break things” mentality undermines healthy maintenance. Brand doesn’t raise the idea—even to dismiss it.
It could be that with Maintenance: Of Everything, Part One Brand is just getting going; that in subsequent volumes he’ll have something more coherent to say; that he’ll raise really hard questions and try to answer them. But given his track record, we might reasonably doubt it. Kesey said Brand cleaves to power; he certainly doesn’t question it.
Lee Vinsel is an associate professor of science, technology, and society at Virginia Tech and host of Peoples & Things, a podcast about human life with technology.