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Why crash test dummies used in car safety tests are still modeled after men

Why crash test dummies used in car safety tests are still modeled after men

Fast Company23-06-2025
Maria Weston Kuhn had one lingering question about the car crash that forced her to have emergency surgery during a vacation in Ireland: Why did she and her mother sustain serious injuries while her father and brother, who sat in the front, emerge unscathed?
'It was a head-on crash and they were closest to the point of contact,' said Kuhn, now 25, who missed a semester of college to recover from the 2019 collision that caused her seat belt to slide off her hips and rupture her intestines by pinning them against her spine. 'That was an early clue that something else was going on.'
When Kuhn returned home to Maine, she found an article her grandma had clipped from Consumer Reports and left on her bed. Women are 73% more likely to be injured in a frontal crash, she learned, yet the dummy used in vehicle tests by the National Highway Traffic Safety Administration dates back to the 1970s and is still modeled almost entirely off the body of a man.
A survivor becomes an activist
Kuhn, who is starting law school at New York University this fall, took action and founded the nonprofit Drive US Forward. Its aim was to raise public awareness and eventually encourage members of Congress to sign onto a bill that would require NHTSA to incorporate a more advanced female dummy into its testing.
The agency has the final word on whether cars get pulled from the market, and the kind of dummy used in its safety tests could impact which ones receive coveted five-star ratings.
'It seems like we have an easy solution here where we can have crash test dummies that reflect an average woman as well as a man,' Sen. Deb Fischer, a Nebraska Republican who has introduced the legislation the past two sessions, told The Associated Press.
Senators from both parties have signed onto Fischer's 'She Drives Act,' and the transportation secretaries from the past two presidential administrations have expressed support for updating the rules.
But for various reasons, the push for new safety requirements has been moving at a sluggish pace. That's particularly true in the U.S., where much of the research is happening and where around 40,000 people are killed each year in car crashes.
Evolution of a crash test dummy
The crash test dummy currently used in NHTSA five-star testing is called the Hybrid III, which was developed in 1978 and modeled after a 5-foot-9, 171-pound man (the average size in the 1970s but about 29 pounds lighter than today's average). What's known as the female dummy is essentially a much smaller version of the male model with a rubber jacket to represent breasts. It's routinely tested in the passenger seat or the back seat but seldom in the driver's seat, even though the majority of licensed drivers are women.
'What they didn't do is design a crash test dummy that has all the sensors in the areas where a woman would be injured differently than a man,' said Christopher O'Connor, president and CEO of the Farmington Hills, Michigan-based Humanetics Group, which has spent more than a decade developing and refining one.
A female dummy from Humanetics equipped with all of the available sensors costs around $1 million, about twice the cost of the Hybrid used now.
But, O'Connor says, the more expensive dummy far more accurately reflects the anatomical differences between the sexes — including in the shape of the neck, collarbone, pelvis, and legs, which one NHTSA study found account for about 80% more injuries by women in a car crash compared to men.
Such physical dummies will always be needed for vehicle safety tests, and to verify the accuracy of virtual tests, O'Connor said.
Europe incorporated the more advanced male dummy developed by Humanetics' engineers, the THOR 50M (based on a 50th percentile man), into its testing procedures soon after Kuhn's 2019 crash in Ireland. Several other countries, including China and Japan, have adopted it as well.
But that model and the female version the company uses for comparison, the THOR 5F (based on a 5th percentile woman), have been met with skepticism from some American automakers who argue the more sophisticated devices may exaggerate injury risks and undercut the value of some safety features such as seat belts and airbags.
A debate over whether more sensors mean more safety
Bridget Walchesky, 19, had to be flown to a hospital, where she required eight surgeries over a month, after a 2022 crash near her home in Sheboygan, Wisconsin, that killed her friend, who was driving. While acknowledging the seat belt likely saved her life, Walchesky said some of the injuries — including her broken collarbone — were the result of it pinning her too tightly, which she views as something better safety testing focused on women could improve.
'Seat belts aren't really built for bodies on females,' Walchesky said. 'Some of my injuries, the way the force hit me, they were probably worsened.'
The Alliance for Automotive Innovation, an industry trade group, said in a statement to the AP that the better way to ensure safety — which it called its top priority — is through upgrades to the existing Hybrid dummy rather than mandating a new one.
'This can happen on a faster timeline and lead to quicker safety improvements than requiring NHTSA to adopt unproven crash test dummy technology,' the alliance said.
Humanetics' THOR dummies received high marks in the vehicle safety agency's early tests. Using cadavers from actual crashes to compare the results, NHTSA found they outperformed the existing Hybrid in predicting almost all injuries — including to the head, neck, shoulders, abdomen and legs.
A separate review by the Insurance Institute for Highway Safety, a research arm funded by auto insurers, was far more critical of the dummy's ability to predict chest injuries in a frontal crash. Despite the vast expansion in the number of sensors, the insurance institute's testing found, the male THOR dummy was less accurate than the current Hybrid dummies, which also had limitations.
'More isn't necessarily better,' said Jessica Jermakian, senior vice president for vehicle research at IIHS. 'You also have to be confident that the data is telling you the right things about how a real person would fare in that crash.'
The slow pace of changing the rules
NHTSA's budget plan commits to developing the female THOR 5F version with the ultimate goal of incorporating it into the testing. But there could be a long wait considering the THOR's male version adopted by other countries is still awaiting final approval in the U.S.
A 2023 report by the Government Accountability Office, which conducts research for Congress, cited numerous 'missed milestones' in NHTSA's development of various crash dummy enhancements — including in the THOR models.
Kuhn acknowledges being frustrated by the slow process of trying to change the regulations. She says she understands why there's reluctance from auto companies if they fear being forced to make widespread design changes with more consideration for women's safety.
'Fortunately, they have very skilled engineers and they'll figure it out,' she said.
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ACV Announces Second Quarter 2025 Results
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About ACV Auctions ACV is on a mission to transform the automotive industry by building the most trusted and efficient digital marketplace and data solutions for sourcing, selling and managing used vehicles with transparency and comprehensive insights that were once unimaginable. ACV offerings include ACV Auctions, ACV Transportation, ACV Capital, ACV MAX, True360, and ClearCar. For more information about ACV, visit Information About Non-GAAP Financial Measures ACV provides supplemental non-GAAP financial measures to its financial results. We use these non-GAAP financial measures, and we believe that they assist our investors to make period-to-period comparisons of our operating performance because they provide a view of our operating results without items that are not, in our view, indicative of our operating results. These non-GAAP financial measures should not be construed as an alternative to GAAP results as the items excluded from the non-GAAP financial measures often have a material impact on our operating results, certain of those items are recurring, and others often recur. Management uses, and investors should consider, our non-GAAP financial measures only in conjunction with our GAAP EBITDA is a financial measure that is not presented in accordance with GAAP. We believe that Adjusted EBITDA, when taken together with our financial results presented in accordance with GAAP, provides meaningful supplemental information regarding our operating performance and facilitates internal comparisons of our historical operating performance on a more consistent basis by excluding certain items that may not be indicative of our business, results of operations or outlook. In particular, we believe that the use of Adjusted EBITDA is helpful to our investors as it is a measure used by management in assessing the health of our business, determining incentive compensation and evaluating our operating performance, as well as for internal planning and forecasting purposes. We define Adjusted EBITDA as net loss, adjusted to exclude: depreciation and amortization; stock-based compensation expense; interest (income) expense; provision for income taxes; and other one-time non-recurring items, when applicable, such as acquisition-related and restructuring expenses. Adjusted EBITDA is presented for supplemental informational purposes only, has limitations as an analytical tool and should not be considered in isolation or as a substitute for financial information presented in accordance with GAAP. Some of these limitations include that (1) it does not properly reflect capital commitments to be paid in the future; (2) although depreciation and amortization are non-cash charges, the underlying assets may need to be replaced and Adjusted EBITDA does not reflect these capital expenditures; (3) it does not consider the impact of stock-based compensation expense, (4) it does not reflect other non-operating income and expenses, including interest income and expense, (5) it does not consider the impact of any contingent consideration liability valuation adjustments, (6) it does not reflect tax payments that may represent a reduction in cash available to us,(7) it does not include the amortization of acquired intangible assets but it does include the revenue that these acquired intangible assets contribute to the enterprise, and (8) it does not reflect other one-time, non-recurring items, when applicable, such as acquisition-related and restructuring expenses. In addition, our use of Adjusted EBITDA may not be comparable to similarly titled measures of other companies because they may not calculate Adjusted EBITDA in the same manner, limiting its usefulness as a comparative measure. Because of these limitations, when evaluating our performance, you should consider Adjusted EBITDA alongside other financial measures, including our net loss and other results stated in accordance with GAAP. Non-GAAP net income (loss), and non-GAAP operating expenses, are financial measures that are not presented in accordance with GAAP, provide investors with additional useful information to measure operating performance and current and future liquidity when taken together with our financial results presented in accordance with GAAP. By providing this information, we believe management and the users of the financial statements are better able to understand the financial results of what we consider to be our continuing operations. We define non-GAAP net income (loss) as net income (loss), adjusted to exclude: stock-based compensation expense, amortization of acquired intangible assets, and other one-time, non-recurring items, when applicable, such as acquisition-related and restructuring expenses. We define non-GAAP operating expenses as operating expenses adjusted to exclude the same items that are excluded from non-GAAP net income (loss). In the calculation of non-GAAP net income (loss) and non-GAAP operating expenses we exclude stock-based compensation expense because of varying available valuation methodologies, subjective assumptions and the variety of equity instruments that can impact our non-cash expense. We believe that providing non-GAAP financial measures that exclude stock-based compensation expense allows for more meaningful comparisons between our operating results from period to period. We exclude amortization of acquired intangible assets from the calculation of non-GAAP net income (loss) and non-GAAP operating expenses. We believe that excluding the impact of amortization of acquired intangible assets allows for more meaningful comparisons between operating results from period to period as the underlying intangible assets are valued at the time of acquisition and are amortized over several years after the acquisition. We exclude contingent consideration liability valuation adjustments associated with the purchase consideration of transactions accounted for as business combinations. We also exclude certain other one-time, non-recurring items, when applicable, such as acquisition-related and restructuring expenses, because we do not consider such amounts to be part of our ongoing operations nor are they comparable to prior period nor predictive of future results. Non-GAAP net income (loss) and non-GAAP operating expenses are presented for supplemental informational purposes only, have limitations as an analytical tool and should not be considered in isolation or as a substitute for financial information presented in accordance with GAAP. 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Our key operating and financial metrics may be calculated in a manner different than similar business metrics used by other GMV - Marketplace GMV is primarily driven by the volume and dollar value of Marketplace Unit transactions. We believe that Marketplace GMV acts as an indicator of our success, signaling satisfaction of dealers and buyers, and the health, scale, and growth of our business. We define Marketplace GMV as the total dollar value of vehicles transacted within the applicable period, excluding any auction and ancillary fees. Marketplace Units - Marketplace Units is a key indicator of our potential for growth in Marketplace GMV and revenue. It demonstrates the overall engagement of our customers and our market share of wholesale transactions in the United States. We define Marketplace Units as the number of vehicles transacted within the applicable period. 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In some cases, you can identify forward-looking statements because they contain words such as 'anticipate,' 'believe,' 'contemplate,' 'continue,' 'could,' 'estimate,' 'expect,' 'intend,' 'may,' 'plan,' 'potential,' 'predict,' 'project,' 'should,' 'target,' 'will' or 'would' or the negative of these words or other similar terms or expressions. You should not rely on forward-looking statements as predictions of future events. The forward-looking statements contained in this presentation are based on ACV's current assumptions, expectations and beliefs and are subject to substantial risks, uncertainties and changes in circumstances that may cause ACV's actual results, performance or achievements to differ materially from those expressed or implied in any forward-looking statement. 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These and other risks and uncertainties are more fully described in our filings with the Securities and Exchange Commission ('SEC'), including in the section entitled 'Risk Factors' in our Form 10-K for the year ended December 31, 2024, filed with the SEC on February 19, 2025. Additional information will be made available in other filings and reports that we may file from time to time with the SEC. New risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties and assumptions, we cannot guarantee future results, levels of activity, performance, achievements, or events and circumstances reflected in the forward-looking statements will occur. The forward-looking statements made in this presentation relate only to events as of the date on which the statements are made. We undertake no obligation to update any forward-looking statements made in this presentation to reflect events or circumstances after the date of this presentation or to reflect new information or the occurrence of unanticipated events, except as required by law. Investor Contact: Tim Foxtfox@ Media Contact: Maura Dugganmduggan@ ACV AUCTIONS CONSOLIDATED STATEMENTS OF OPERATIONS(Unaudited)(in thousands, except per share data) Three months ended June 30, Six months ended June 30, 2025 2024 2025 2024 Marketplace and service revenue $ 175,995 $ 144,126 $ 341,932 $ 273,940 Customer assurance revenue 17,708 16,498 34,468 32,373 Total revenue 193,703 160,624 376,400 306,313 Marketplace and service cost of revenue (excluding depreciation & amortization) 74,319 64,253 143,721 119,946 Customer assurance cost of revenue (excluding depreciation & amortization) 16,909 14,558 30,886 27,372 Operations and technology 45,801 39,694 89,991 77,763 Selling, general, and administrative 52,972 51,912 111,990 105,765 Depreciation and amortization 10,897 8,848 21,438 16,635 Total operating expenses 200,898 179,265 398,026 347,481 Loss from operations (7,195 ) (18,641 ) (21,626 ) (41,168 ) Interest income 2,152 2,329 4,041 5,360 Interest expense (2,286 ) (606 ) (4,196 ) (1,141 ) Total other income (expense) (134 ) 1,723 (155 ) 4,219 Loss before income taxes (7,329 ) (16,918 ) (21,781 ) (36,949 ) (31 ) 145 334 585 Net loss $ (7,298 ) $ (17,063 ) $ (22,115 ) $ (37,534 ) Weighted-average shares - basic and diluted 170,472 164,384 169,415 163,637 Net loss per share - basic and diluted $ (0.04 ) $ (0.10 ) $ (0.13 ) $ (0.23 ) ACV AUCTIONS CONSOLIDATED BALANCE SHEETS(Unaudited)(in thousands) June 30,2025 December 31,2024 Assets Cash and cash equivalents $ 258,365 $ 224,065 Marketable securities 46,368 46,036 Trade receivables (net of allowance of $4,368 and $6,372) 209,880 168,770 Finance receivables (net of allowance of $5,097 and $4,191) 207,068 139,045 Other current assets 16,254 15,281 Total current assets 737,935 593,197 Property and equipment (net of accumulated depreciation of $5,804 and $5,227) 10,135 7,625 Goodwill 183,676 180,478 Acquired intangible assets (net of amortization of $34,998 and $28,972) 86,206 90,816 Capitalized software (net of amortization of $52,842 and $38,499) 75,648 68,571 Other assets 44,673 43,462 Total assets $ 1,138,273 $ 984,149 Liabilities and Stockholders' Equity Accounts payable $ 430,646 $ 345,605 Accrued payroll 12,100 16,725 Accrued other liabilities 19,912 18,836 Total current liabilities 462,658 381,166 Long-term debt 186,500 123,000 Other long-term liabilities 40,332 39,979 Total liabilities 689,490 544,145 Commitments and Contingencies Preferred Stock — — Common Stock 172 168 Common Stock - Class B — — Additional paid-in capital 971,390 944,891 Accumulated deficit (524,430 ) (502,315 ) Accumulated other comprehensive income (loss) 1,651 (2,740 ) Total stockholders' equity 448,783 440,004 Total liabilities and stockholders' equity $ 1,138,273 $ 984,149 ACV AUCTIONS CONSOLIDATED STATEMENTS OF CASH FLOWS(Unaudited)(in thousands) Six months ended June 30, 2025 2024 Net loss $ (22,115 ) $ (37,534 ) Adjustments to reconcile net loss to net cash provided by operating activities: Depreciation and amortization 21,449 16,682 Stock-based compensation expense, net of amounts capitalized 32,028 29,794 Provision for bad debt 3,111 5,055 Other non-cash, net 2,266 119 Changes in operating assets and liabilities, net of effects from purchases of businesses: Trade receivables (41,714 ) (19,158 ) Other operating assets (1,059 ) 3,036 Accounts payable 85,423 37,641 Other operating liabilities 950 11,856 Net cash provided by operating activities 80,339 47,491 Net increase in finance receivables (71,564 ) (1,851 ) Purchases of property and equipment (4,205 ) (2,872 ) Capitalization of software costs (17,932 ) (14,855 ) Purchases of marketable securities (24,833 ) (21,607 ) Maturities and redemptions of marketable securities 24,888 69,699 Sales of marketable securities — 122,698 Acquisition of businesses (net of cash acquired) — (155,209 ) Net cash used in investing activities (93,646 ) (3,997 ) Proceeds from long term debt 220,000 340,000 Payments towards long term debt (156,500 ) (345,000 ) Payment of debt issuance costs (1,457 ) (1,702 ) Proceeds from exercise of stock options 531 6,812 Payment of RSU tax withholdings in exchange for common shares surrendered by RSU holders (17,636 ) (13,110 ) Proceeds from employee stock purchase plan 2,534 1,998 Other financing activities (74 ) (23 ) Net cash provided by (used in) financing activities 47,398 (11,025 ) Effect of exchange rate changes on cash, cash equivalents, and restricted cash 209 (68 ) Net increase in cash, cash equivalents, and restricted cash 34,300 32,401 224,065 182,571 $ 258,365 $ 214,972 The following table presents a reconciliation of non-GAAP net income (loss) to net income (loss), the most directly comparable financial measure stated in accordance with GAAP, for the periods presented: Three months ended June 30, Six months ended June 30, 2025 2024 2025 2024 Net income (loss) $ (7,298 ) $ (17,063 ) $ (22,115 ) $ (37,534 ) Stock-based compensation 15,454 14,965 32,028 29,794 Amortization of acquired intangible assets 2,591 3,013 5,364 5,226 Amortization of capitalized stock based compensation 1,504 980 2,967 1,908 Acquisition-related costs — 1,187 403 3,306 Litigation-related costs (1) — — 1,100 1,553 Other — 145 — 189 Non-GAAP Net income (loss) $ 12,251 $ 3,227 $ 19,747 $ 4,442 (1) Litigation-related costs are related to an anti-competition case which we do not consider to be representative of our underlying operating performance The following table presents a reconciliation of Adjusted EBITDA to net income (loss), the most directly comparable financial measure stated in accordance with GAAP, for the periods presented: Three months ended June 30, Six months ended June 30, 2025 2024 2025 2024 Adjusted EBITDA Reconciliation Net income (loss) $ (7,298 ) $ (17,063 ) $ (22,115 ) $ (37,534 ) Depreciation and amortization 10,904 8,880 21,450 16,682 Stock-based compensation 15,454 14,965 32,028 29,794 Interest expense (income) 134 (1,723 ) 155 (4,219 ) Provision for income taxes (31 ) 145 334 585 Acquisition-related costs — 1,187 403 3,306 Litigation-related costs (1) — — 1,100 1,553 Other (586 ) 687 (870 ) 1,180 Adjusted EBITDA $ 18,577 $ 7,078 $ 32,485 $ 11,347 (1) Litigation-related costs are related to an anti-competition case which we do not consider to be representative of our underlying operating performance The following table presents a reconciliation of Non-GAAP total operating expenses (excluding cost of revenue) to GAAP total operating expenses, the most directly comparable financial measure stated in accordance with GAAP, for the periods presented: Three months ended June 30, Six months ended June 30, 2025 2024 2025 2024 Total operating expenses $ 200,898 $ 179,265 $ 398,026 $ 347,481 Non-GAAP Adjustments: Marketplace and service cost of revenue (excluding depreciation & amortization) 74,319 64,253 143,721 119,946 Customer assurance cost of revenue (excluding depreciation & amortization) 16,909 14,558 30,886 27,372 Stock-based compensation 15,173 14,759 31,442 29,339 Amortization of acquired intangible assets 2,591 3,013 5,364 5,226 Amortization of capitalized stock-based compensation 1,504 980 2,967 1,908 Acquisition-related costs — 1,187 403 3,307 Other — 145 1,100 1,743 Non-GAAP Total operating expenses (excluding cost of revenue) $ 90,402 $ 80,370 $ 182,143 $ 158,640 The following table presents a reconciliation of non-GAAP net income (loss) to GAAP net income (loss), the most directly comparable financial measure stated in accordance with GAAP, for the periods presented (in millions): Three months ended September 30, 2025 Year ended December 31, 2025 Non-GAAP net income (loss) to net income (loss) guidance Reconciliation Net income (loss) ($13) - ($11) ($51) - ($47) Non-GAAP Adjustments: Stock-based compensation $19 $70 Intangible amortization $3 $11 Amortization of capitalized stock-based compensation $2 $6 Other — $2 Non-GAAP net income $11 - $13 $38 - $42 Error in retrieving data Sign in to access your portfolio Error in 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Ford to invest $5 billion in EV production. Here's what to know.
Ford to invest $5 billion in EV production. Here's what to know.

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Ford to invest $5 billion in EV production. Here's what to know.

Ford is investing $5 billion to change the way it makes electric vehicles, a move the automaker says will allow it to manufacture models starting at $30,000 — far less than the current average price for an EV. The Dearborn, Michigan-based company on Monday said it will invest $2 billion to modernize its Louisville Assembly Plant and another $3 billion to build a new battery plant in Michigan, part of its push to produce more affordable EVs. Switch Auto Insurance and Save Today! Great Rates and Award-Winning Service The Insurance Savings You Expect Affordable Auto Insurance, Customized for You The company unveiled its new "universal EV platform" at a Monday event, with Ford CEO Jim Farley calling it "the most radical change on how we design and how we build vehicles at Ford since the Model T," which Ford introduced in 1908. According to Ford, the new assembly line will be structured more like an "assembly tree," with three different lines that converge into one, rather than a single assembly belt. "This way of building a vehicle, we're confident, is the first time anyone's done this anywhere in the world," said Doug Field, Ford's EV chief of digital and design, at Monday's event. The company said the design will lead to a quicker, smoother assembly process and improve ergonomics for employees through a less obstructive layout. "Ford's announcement is very ambitious, because it includes both a new production process and a new vehicle," said Patrick Anderson, founder of Michigan-based consulting firm Anderson Economic Group, in an email to CBS MoneyWatch. "If they can actually pull off a production line that has 40% fewer workstations and 20% fewer parts, it will be worthy of the 'Model T moment' claim. Ford's first EV from the new system The first product of this new production system will be a four-door midsize truck, which will debut in 2027. Farley said on Monday that the new vehicle will accommodate five people and feature a "frunk" — a front storage compartment — as well as a pickup truck bed. The vehicle will start at $30,000. By comparison, the average price for a new electric vehicle in July was about $56,000, according to Kelley Blue Book. Field touted the new vehicle's charging capabilities, referring to the truck as a "mobile power plant." "Outlets in the back can give you high power and let you plug in anything from tools to a refrigerator, and it can provide backup power for your home," he said. The midsize electric truck could be produced up to 40% faster than other vehicles at the Louisville Assembly Plant due to the new process, Ford said. In another effort to lower costs, the auto company is also reducing the number of components that go into each car. Vehicles produced on the "universal EV platform" will have 20% fewer parts than a traditional vehicle, Ford said. The company will also use smaller cobalt and nickel-free batteries that will allow it to make "cost gains," according to a video shared by Ford. Anderson said that Ford has its work cut out for them given that the new truck will need to be competitively priced and economical. According to the auto industry expert, the cost of charging EV trucks currently on the market is often much higher than the price at the pump for gas-powered versions. A report from the Anderson Economic Group shows pickup trucks drivers in New York, California and Michigan face "significantly higher costs" if they rely on an EV. A successfully lower-cost truck model, however, could spur a new chapter for the company in its manufacturing of EVs. "If Ford shows the industry it can build and sell a reliable compact EV truck for $30,000, it will sell a lot of them, and open the door to making sedans using the new production process," Anderson said. Derek and the Dominos co-founder Bobby Whitlock dies Artisan bakers sparking sourdough boom At least 1 dead, dozens injured and others trapped in U.S. Steel plant explosion in Pennsylvania Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data

Denali Therapeutics Reports Second Quarter 2025 Financial Results and Business Highlights
Denali Therapeutics Reports Second Quarter 2025 Financial Results and Business Highlights

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Denali Therapeutics Reports Second Quarter 2025 Financial Results and Business Highlights

Tividenofusp alfa BLA for Hunter syndrome accepted for priority review and assigned PDUFA target action date of January 5, 2026; company preparing for commercial launch DNL126 accelerated approval path for Sanfilippo syndrome Type A aligned with FDA; Phase 1/2 study nearing completion of enrollment; planning underway for a global Phase 3 confirmatory study On track to submit regulatory applications in 2025 to begin clinical testing of one to two additional TransportVehicleTM (TV)-enabled programs Preclinical research on ATV:Abeta program for Alzheimer's disease published in the journal Science SOUTH SAN FRANCISCO, Calif., Aug. 11, 2025 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (Nasdaq: DNLI) today reported financial results for the second quarter ended June 30, 2025, and provided business highlights. 'The FDA's priority review of our BLA for tividenofusp alfa and alignment on an accelerated approval path for DNL126 are key milestones highlighting the potential of our Transport Vehicle (TV) platform to catalyze a new class of blood-brain barrier-crossing therapeutics,' said Ryan Watts, Ph.D., CEO of Denali Therapeutics. 'With launch readiness in motion and a growing portfolio of TV-enabled enzyme, antibody, and oligonucleotide programs, Denali is poised to deliver meaningful treatments for people living with lysosomal, neurodegenerative, and other serious diseases.' Second Quarter 2025 and Recent Program Updates CLINICAL PROGRAMS Tividenofusp alfa (DNL310, ETV:IDS) for Hunter syndrome (MPS II) In July 2025, Denali announced that the U.S. Food and Drug Administration (FDA) accepted its Biologics License Application (BLA) for tividenofusp alfa for priority review, assigning a Prescription Drug User Fee Act (PDUFA) target action date of January 5, 2026. The BLA seeks accelerated approval based on a data package including results from the Phase 1/2 study in individuals with Hunter syndrome. Tividenofusp alfa is an investigational, next-generation enzyme replacement therapy designed to cross the blood-brain barrier (BBB) and deliver the iduronate-2-sulfatase (IDS) enzyme throughout the body and brain. The FDA previously granted tividenofusp alfa Breakthrough Therapy, Fast Track, Orphan Drug, and Rare Pediatric Disease designations. Denali continues to prepare for commercial launch and is conducting the Phase 2/3 COMPASS study to support global regulatory submissions. DNL126 (ETV:SGSH) for Sanfilippo syndrome type A (MPS IIIA) Today, Denali announced that it has reached alignment with the FDA's Center for Drug Evaluation and Research (CDER) that cerebrospinal fluid heparan sulfate (CSF HS) may be considered a reasonably likely surrogate endpoint to predict clinical benefit and may therefore be used to support accelerated approval of DNL126 for MPS IIIA. Additional 49-week data from the ongoing open-label Phase 1/2 study are consistent with previously announced 25-week data, demonstrating a significant reduction in CSF HS from baseline, including normalization, and a safety profile that supports continued development. Enrollment in the Phase 1/2 study is nearly complete, and planning is underway for a confirmatory global Phase 3 study. TAK-594/DNL593 (PTV:PGRN) for GRN-related frontotemporal dementia Denali and Takeda continue their collaboration to develop DNL593, an investigational therapeutic designed to deliver progranulin across the BBB for the treatment of granulin (GRN) mutation-associated frontotemporal dementia (FTD-GRN). A Phase 1/2 study is ongoing. BIIB122/DNL151 (small molecule LRRK2 inhibitor) for the treatment of Parkinson's disease (PD) Denali and Biogen are co-developing LRRK2 inhibitors for Parkinson's disease. In May 2025, Biogen announced that the Phase 2b LUMA study of BIIB122 completed enrollment, with a readout expected in 2026. Denali is also conducting the Phase 2a BEACON study focused on LRRK2-associated PD. IND-ENABLING STAGE PROGRAMS Denali expects to submit regulatory applications to begin clinical testing of one to two TV-enabled programs each year over the next three years across its Enzyme TV (ETV), Antibody TV (ATV), and Oligonucleotide TV (OTV) franchises. The most advanced programs include: DNL952 (ETV:GAA) for Pompe disease; DNL111 (ETV:GCase) for Parkinson's/Gaucher disease; DNL622 (ETV:IDUA) for MPS I; DNL921 (ATV:Abeta) for Alzheimer's disease; DNL628 (OTV:MAPT) for Alzheimer's disease; and DNL422 (OTV:SNCA) for Parkinson's disease. Denali announced publication of preclinical data on ATV:Abeta in the August 7, 2025, issue of the journal Science. The research demonstrated that delivering an anti-amyloid beta antibody across the BBB using Denali's TV platform improved brain distribution and reduced the risk of amyloid-related imaging abnormality (ARIA) in a mouse model of Alzheimer's disease, compared to conventional antibody treatment. The findings suggest that TV platform-enabled brain delivery of immunotherapy bypasses amyloid-laden large vessels by traveling through smaller capillaries, offering a potential strategy to mitigate ARIA risk seen with first-generation anti-amyloid therapies. The Science article can be accessed here. Participation in Upcoming Investor Conferences Cantor Global Healthcare Conference 2025, September 3 - 5 (New York City) Morgan Stanley 23rd Annual Global Healthcare Conference, September 8 - 10 (New York City) Baird 2025 Global Healthcare Conference, September 9 - 10 (New York City) H.C. Wainwright 27th Annual Global Investment Conference, September 8 - 10 (New York City) Deutsche Bank BioPharm Corporate Day, September 18 - 19 (Austria) Stifel 2025 Healthcare Conference, November 11 - 13 (New York City) Jefferies Global Healthcare Conference, November 17 - 20 (London) Second Quarter 2025 Financial Results Net loss was $124.1 million for the quarter ended June 30, 2025, compared to net loss of $99.0 million for the quarter ended June 30, 2024. Total research and development expenses were $102.7 million for the quarter ended June 30, 2025, compared to $91.4 million for the quarter ended June 30, 2024. The increase of approximately $11.3 million was attributable to an increase of $7.3 million in TV program external research and development expenses, primarily driven by increased spend on multiple preclinical programs, and increases of $7.6 million and $6.2 million in other research and development expenses and personnel-related expenses, respectively, both driven by the commencement of operations at Denali's large molecule manufacturing facility in Salt Lake City, Utah. These increases were partially offset by a $9.8 million decrease in small molecule programs, primarily due to the winding down of activities related to the Phase 2/3 HEALEY ALS Platform Trial. General and administrative expenses were $32.3 million for the quarter ended June 30, 2025, compared to $25.2 million for the quarter ended June 30, 2024. The increase of $7.1 million was primarily driven by activities related to preparations for a potential commercial launch for tividenofusp alfa. Cash, cash equivalents, and marketable securities were approximately $977.4 million as of June 30, 2025. About Denali Therapeutics Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for the treatment of neurodegenerative diseases and lysosomal storage diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the BBB, and guiding development through biomarkers that demonstrate target and pathway engagement. Denali is based in South San Francisco. For additional information, please visit Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding expectations for Denali's TV platform and its therapeutics and commercial potential; statements made by Denali's Chief Executive Officer; plans, timelines, and expectations relating to DNL310, including the PDUFA target action date and the timing, likelihood of, and scope of regulatory approval, the ongoing global Phase 2/3 COMPASS study and the likelihood of global approvals, and planned commercial launch; plans, timelines, and expectations related to DNL126, including enrollment in the ongoing Phase 1/2 study, plans regarding the confirmatory global Phase 3 study, planned engagement with the FDA, and the likelihood and scope of regulatory approvals; plans regarding DNL593 and the ongoing Phase 1/2 study; plans, timelines, and expectations regarding DNL151, including with respect to the ongoing Phase 2b LUMA study and the timing and likelihood of readout, and the ongoing Phase 2a BEACON study; plans and expectations for Denali's preclinical programs, including the timing of advancement to clinical studies; the findings from Denali's recent Science publication and their therapeutic potential regarding ARIA risk; Denali's participation in upcoming investor conferences; and Denali's future operating expenses and anticipated cash runway. All drugs currently being developed by Denali are investigational and have not received regulatory approval for any indication. Actual results are subject to risks and uncertainties and may differ materially from those indicated by these forward-looking statements as a result of these risks and uncertainties, including but not limited to, risks related to: the impact of adverse economic conditions, tariffs, and inflation on Denali's business and operations; the occurrence of any event, change, or other circumstance that could give rise to the termination of Denali's agreements with Sanofi, Takeda, Biogen, or other collaborators; Denali's transition to a late-stage clinical drug development company; Denali's and its collaborators' ability to complete the development and, if approved, commercialization of its product candidates; Denali's and its collaborators' ability to enroll patients in its ongoing and future clinical trials; Denali's reliance on third parties for the manufacture and supply of its product candidates for clinical trials; Denali's dependence on successful development of its blood-brain barrier platform technology and its programs and product candidates; Denali's and its collaborators' ability to conduct or complete clinical trials on expected timelines; the risk that preclinical profiles of Denali's product candidates may not translate in clinical trials; the potential for clinical trials to differ from preclinical, early clinical, preliminary or expected results; the risk of significant adverse events, toxicities, or other undesirable side effects; the uncertainty that product candidates will receive regulatory approval necessary to be commercialized; Denali's ability to continue to create a pipeline of product candidates or commercialize products; developments relating to Denali's competitors and its industry, including competing product candidates and therapies; Denali's ability to obtain, maintain, or protect intellectual property rights related to its product candidates; implementation of Denali's strategic plans for its business, product candidates, and blood-brain barrier platform technology; Denali's ability to obtain additional capital to finance its operations, as needed; Denali's ability to accurately forecast future financial results and hedge against financial risk in the current environment; and other risks and uncertainties, including those described in Denali's most recent Annual Report and Quarterly Reports on Forms 10-K and 10-Q filed with the Securities and Exchange Commission (SEC) on February 27, 2025 and May 6, 2025, and Denali's future reports to be filed with the SEC. Denali does not undertake any obligation to update or revise any forward-looking statements, to conform these statements to actual results, or to make changes in Denali's expectations, except as required by law. Denali Therapeutics Consolidated Statements of Operations(Unaudited)(In thousands, except share and per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2025 2024 2025 2024 Operating expenses: Research and development $ 102,696 $ 91,399 218,923 198,415 General and administrative 32,267 25,194 61,620 50,430 Total operating expenses 134,963 116,593 280,543 248,845 Gain from divestiture of small molecule programs — — — 14,537 Loss from operations (134,963 ) (116,593 ) (280,543 ) (234,308 ) Interest and other income, net 10,844 17,567 23,454 33,480 Net loss $ (124,119 ) $ (99,026 ) $ (257,089 ) $ (200,828 ) Net loss per share, basic and diluted $ (0.72 ) $ (0.59 ) $ (1.50 ) $ (1.26 ) Weighted average number of shares outstanding, basic and diluted 171,449,847 168,831,329 171,336,568 159,117,759 Denali Therapeutics Consolidated Balance Sheets(Unaudited)(In thousands) June 30, 2025 December 31, 2024 Assets Current assets: Cash and cash equivalents $ 141,207 $ 174,960 Short-term marketable securities 757,745 657,371 Prepaid expenses and other current assets 35,754 32,105 Total current assets 934,706 864,436 Long-term marketable securities 78,463 359,373 Property and equipment, net 58,717 55,236 Finance lease right-of-use asset 50,363 47,533 Operating lease right-of-use asset 21,022 22,861 Other non-current assets 22,970 24,741 Total assets $ 1,166,241 $ 1,374,180 Liabilities and stockholders' equity Current liabilities: Accounts payable $ 10,844 $ 11,137 Accrued compensation 12,068 24,728 Accrued clinical and other research & development costs 23,379 22,822 Accrued manufacturing costs 9,028 12,779 Operating lease liability, current 8,871 8,308 Deferred research and development funding liability, current 19,861 14,129 Other accrued costs and current liabilities 7,006 8,305 Total current liabilities 91,057 102,208 Operating lease liability, less current portion 32,110 36,673 Finance lease liability, less current portion 5,577 5,615 Deferred research funding and development liability, less current portion 10,444 — Total liabilities 139,188 144,496 Total stockholders' equity 1,027,053 1,229,684 Total liabilities and stockholders' equity $ 1,166,241 $ 1,374,180 Investor Contact:Laura Hansen, Media Contact:Erin Pattonepatton@ in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data

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