5 hand signals

5 hand signals Palvella Therapeutics to debut on Nasdaq under the ticker symbol “PVLA” as a publicly traded rare disease biopharmaceutical company advancing a late clinical-stage pipeline and a platform for treating serious, rare genetic diseases Strong balance sheet with approximately $80.0 million of cash and cash equivalents, including proceeds from a PIPE financing co-led by BVF Partners, L.P. and Frazier Life Sciences Cash expected to fund operations into the second half of 2027, including through Phase 3 SELVA clinical trial of QTORINTM 3.9% rapamycin anhydrous gel (QTORINTM rapamycin) for the treatment of microcystic lymphatic malformations (microcystic LMs) and Phase 2 clinical trial in cutaneous venous malformations (cutaneous VMs) Microcystic LMs is a chronically debilitating and lifelong genetic disease affecting an estimated more than 30,000 diagnosed patients in the U.S. QTORINTM rapamycin has the potential to be the first approved therapy and standard of care in the U.S. for microcystic LMs and cutaneous VMs WAYNE, Pa., Dec. 13, 2024 (GLOBE NEWSWIRE) -- Palvella Therapeutics, Inc. (Palvella), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare genetic skin diseases for which there are no U.S. Food and Drug Administration (FDA)-approved therapies, today announced the completion of its previously announced merger with Pieris Pharmaceuticals, Inc. (Pieris). The combined company will operate under the name Palvella Therapeutics, Inc., and its shares are expected to begin trading on the Nasdaq Capital Market on December 16, 2024, under the ticker symbol "PVLA". Palvella will continue to be led by Wes Kaupinen, its Founder and Chief Executive Officer, and other members of the Palvella management team. The transaction was approved by Pieris stockholders at a special meeting held on December 11, 2024, and the transaction had been previously approved by Palvella stockholders. "With strong support from leading healthcare-dedicated investors, Palvella is well positioned to enter the public markets and pursue our vision of becoming the leading rare disease company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare genetic skin diseases," said Mr. Kaupinen. “This transaction will enable us to accelerate late-stage development of QTORINTM rapamycin, our lead product candidate, for microcystic LMs and cutaneous VMs while also further advancing additional novel product candidates from our QTORINTM platform." Concurrent with the merger, Palvella completed a previously announced oversubscribed $78.9 million private placement co-led by BVF Partners, L.P., an existing investor, and Frazier Life Sciences, a new investor, and with participation from a syndicate of leading healthcare-dedicated investors. Additional new investors include Blue Owl Healthcare Opportunities, Nantahala Capital, DAFNA Capital Management, ADAR1 Capital Management, and a healthcare dedicated fund. Existing investors Samsara BioCapital, Petrichor, CAM Capital, Ligand Pharmaceuticals, Integrated Finance Group (an AscellaHealth partner company), BioAdvance, and Gore Range Capital also participated in the financing. Palvella's cash and cash equivalents of approximately $80.0 million is expected to fund operations into the second half of 2027, including through results from the SELVA Phase 3 clinical trial of QTORINTM rapamycin for the treatment of microcystic LMs and Phase 2 clinical trial of QTORINTM rapamycin in cutaneous VMs. Palvella’s research team developed QTORINTM, a patented and versatile platform designed to generate novel topical therapies that penetrate the deep layers of the skin to locally treat a broad spectrum of serious, rare genetic skin diseases. Well-accepted mechanisms of action of rapamycin and other therapeutic agents represent potential therapies for rare genetic skin diseases. However, the adverse event profile of those agents through systemic exposure poses significant barriers to patient adoption. Palvella’s QTORINTM product candidates are designed for targeted, localized delivery of therapeutic agents to pathogenic tissue of interest while minimizing systemic absorption and thereby reducing the risk of unwanted adverse events associated with systemic therapy. Palvella's lead product candidate QTORINTM rapamycin is a novel, patented 3.9% rapamycin anhydrous gel currently under development for the treatment of microcystic LMs, cutaneous VMs, and other serious, functionally debilitating skin diseases driven by the overactivation of the mammalian target of rapamycin (mTOR) pathway. QTORINTM rapamycin has received FDA Breakthrough Therapy Designation, Fast Track Designation, and Orphan Drug Designation for microcystic LMs and is the recent recipient of up to a $2.6 million FDA Orphan Products Grant. QTORINTM rapamycin has also received Fast Track Designation for venous malformations. QTORINTM rapamycin is protected by issued composition patents covering anhydrous gel formulations of rapamycin, as well as methods of use, in the U.S., Japan, Australia, China and Israel and pending patent applications broadly covering anhydrous gel formulations of rapamycin, as well as methods of use, in the U.S. and other countries. In the third quarter of 2024, Palvella initiated SELVA, a 24-week, Phase 3, single-arm, baseline-controlled clinical trial of QTORINTM rapamycin administered once daily for the treatment of microcystic LMs. The primary efficacy endpoint is the change from baseline in the overall microcystic LM Investigator Global Assessment (mLM-IGA) at week 24. The Phase 3 study is enrolling approximately 40 subjects, age six or older, at leading vascular anomaly centers across the U.S. Transaction Details Based on the final exchange ratio of approximately 0.30946 shares of Pieris common stock for each share of Palvella common stock, at the closing of the merger, there are approximately 13.95 million shares of the combined company's common stock outstanding on a diluted basis, with prior Pieris stockholders owning approximately 11% on a diluted basis and prior Palvella stockholders (including investors in the private placement) holding approximately 89% of the combined company's outstanding common stock on a diluted basis. In connection with the closing of the merger, Pieris issued a non-transferable contingent value right (CVR) to Pieris shareholders of record immediately prior to the closing, which does not include the former holders of shares of Palvella or the private financing investors. Holders of the CVR will be entitled to receive payments from proceeds received by the combined company, if any, under Pieris' existing partnership agreements with Pfizer and Boston Pharmaceuticals, in addition to other potential licensing agreements involving certain of Pieris' legacy assets, as well as certain potential payments related to historical research and development tax credits, which may or may not be realized. TD Cowen served as lead placement agent and Cantor served as a placement agent for Palvella's concurrent financing. Troutman Pepper Hamilton Sanders LLP served as legal counsel to Palvella. Cooley LLP served as legal counsel to the placement agents. Stifel served as the exclusive financial advisor to Pieris and Mintz, Levin, Cohn, Ferris, Glovsky, and Popeo, P.C. served as legal counsel to Pieris. About Microcystic Lymphatic Malformations Microcystic LMs are a rare, chronically debilitating genetic disease caused by dysregulation of the phosphatidylinositol 3-kinase (PI3K)/mTOR pathway. The disease is characterized by malformed lymphatic vessels that protrude through the skin and persistently leak lymph fluid (lymphorrhea) and bleed, often leading to recurrent serious infections and cellulitis that can cause hospitalization. The natural history of microcystic LMs are persistent and progressive without spontaneous resolution, with symptoms generally worsening during life, including increases in the number and size of malformed vessels that lead to complications and lifetime morbidity. There are currently no FDA-approved treatments for the estimated more than 30,000 diagnosed patients with microcystic LMs in the United States. About Palvella Therapeutics Founded and led by rare drug disease drug development veterans, Palvella Therapeutics (Nasdaq: PVLA) is a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare genetic skin diseases for which there are no FDA-approved therapies. Palvella is developing a broad pipeline of product candidates based on its patented QTORINTM platform, with an initial focus on serious, rare genetic skin diseases, many of which are lifelong in nature. Palvella’s lead product candidate, QTORINTM 3.9% rapamycin anhydrous gel (QTORINTM rapamycin), is currently in the Phase 3 SELVA clinical trial in microcystic lymphatic malformations (microcystic LMs) and a Phase 2 trial in cutaneous venous malformations. For more information, please visit www.palvellatx.com or follow the Company on LinkedIn. QTORINTM rapamycin is for investigational use only and has not been approved or cleared by the FDA or by any other regulatory agency. This press release contains forward-looking statements (including within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended (Securities Act)). These statements may discuss goals, intentions, and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current beliefs of the management of Palvella and Pieris, as well as assumptions made by, and information currently available to, management of Palvella and Pieris. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” and other similar expressions or the negative or plural of these words, or other similar expressions that are predictions or indicate future events or prospects, although not all forward-looking statements contain these words. Statements that are not historical facts are forward-looking statements. Forward-looking statements include, but are not limited to, the sufficiency of the combined company’s capital resources; the combined company’s cash runway; the expected timing of the closing of the proposed transactions; statements regarding the potential of, and expectations regarding, Palvella’s programs, including QTORINTM rapamycin, and its research-stage opportunities, including its expected therapeutic potential and market opportunity; the expected timing of initiating, as well as the design of Palvella’s Phase 2 clinical trial of QTORINTM rapamycin in cutaneous venous malformations. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: the limited operating history of each company; the significant net losses incurred since inception; the ability to raise additional capital to finance operations; the ability to advance product candidates through preclinical and clinical development; the ability to obtain regulatory approval for, and ultimately commercialize, Palvella’s product candidates, including QTORINTM rapamycin; the outcome of early clinical trials for Palvella’s product candidates, including the ability of those trials to satisfy relevant governmental or regulatory requirements; the fact that data and results from clinical studies may not necessarily be indicative of future results; Palvella’s limited experience in designing clinical trials and lack of experience in conducting clinical trials; the ability to identify and pivot to other programs, product candidates, or indications that may be more profitable or successful than Palvella’s current product candidates; the substantial competition Palvella faces in discovering, developing, or commercializing products; the negative impacts of the global events on operations, including ongoing and planned clinical trials and ongoing and planned preclinical studies; the ability to attract, hire, and retain skilled executive officers and employees; the ability of Palvella and Pieris to protect their respective intellectual property and proprietary technologies; reliance on third parties, contract manufacturers, and contract research organizations. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors included in Pieris’ most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K filed with the SEC, as well as the registration statement on Form S-4 filed with the SEC by Pieris in connection with the merger. Palvella and Pieris can give no assurance that the conditions to the proposed transactions will be satisfied. Except as required by applicable law, Palvella and Pieris undertake no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. This press release contains hyperlinks to information that is not deemed to be incorporated by reference into this press release. Palvella Therapeutics Contact Information Investors Wesley H. Kaupinen Founder and CEO, Palvella Therapeutics wes.kaupinen@palvellatx.com Media Stephanie Jacobson Managing Director, Argot Partners palvella@argotpartners.comMcDonald’s pulls beloved menu items due to major issue

Travis Hunter and Ashton Jeanty give this year's Heisman Trophy ceremony a different vibeNEW YORK (AP) — U.S. stock indexes reached more records after tech companies talked up how much artificial intelligence is boosting their results. The S&P 500 climbed 0.6% Wednesday to add to what looks to be one of its best years of the millennium. The Dow Jones Industrial Average gained 0.7%, while the Nasdaq composite added 1.3% to its own record. Salesforce pulled the market higher after highlighting its artificial-intelligence offering for customers. Marvell Technology jumped even more after saying it’s seeing strong demand from AI. Treasury yields eased, while bitcoin climbed after President-elect Donald Trump nominated a crypto advocate to head the Securities and Exchange Commission. THIS IS A BREAKING NEWS UPDATE. AP’s earlier story follows below. NEW YORK (AP) — U.S. stock indexes are rising toward more records Wednesday after tech companies talked up how much of a boost they're getting from artificial intelligence . The S&P 500 climbed 0.5% to add to what looks to be one of its best years of the millennium. It’s on track to set an all-time high for the 56th time this year after coming off 10 gains in the last 11 days . The Dow Jones Industrial Average was up 252 points, or 0.6%, with an hour remaining in trading, while the Nasdaq composite was adding 1.2% to its own record. Salesforce helped pull the market higher after delivering stronger revenue for the latest quarter than analysts expected, though its profit fell just short. CEO Mark Benioff highlighted the company’s artificial-intelligence offering for customers, saying “the rise of autonomous AI agents is revolutionizing global labor, reshaping how industries operate and scale.” The stock of the company, which helps businesses manage their customers, rose 9.3%. Marvell Technology jumped even more after delivering better results than expected, up 23.2%. CEO Matt Murphy said the semiconductor supplier is seeing strong demand from AI and gave a forecast for profit in the upcoming quarter that topped analysts’ expectations. They helped offset a 9.8% drop for Foot Locker, which reported profit and revenue that fell short of analysts’ expectations. CEO Mary Dillon said the company is taking a more cautious view, and it cut its forecasts for sales and profit this year. Dillon pointed to how keen customers are for discounts and how soft demand has been outside of Thanksgiving week and other key selling periods. Retailers overall have offered mixed signals about how resilient U.S. shoppers can remain. Their spending has been one of the main reasons the U.S. economy has avoided a recession that earlier seemed inevitable because of high interest rates brought by the Federal Reserve to crush inflation. But shoppers are now contending with still-high prices and a slowing job market . This week’s highlight for Wall Street will be Friday’s jobs report from the U.S. government, which will show how many people employers hired and fired last month. A narrower report released on Wednesday morning may have offered a preview of it. The report from ADP suggested employers in the private sector increased their payrolls by less last month than economists expected. Hiring in manufacturing was the weakest since the spring, according to Nela Richardson, chief economist at ADP. The report strengthened traders’ expectations that the Fed will cut its main interest rate again when it meets in two weeks. The Fed began easing its main interest rate from a two-decade high in September, hoping to offer more support for the job market. The central bank had appeared set to continue cutting rates into next year, but the election of Donald Trump has scrambled Wall Street’s expectations somewhat. Trump’s preference for higher tariffs and other policies could lead to higher economic growth and inflation , which could alter the Fed’s plans . Fed Chair Jerome Powell said Wednesday that the central bank can afford to cut its benchmark rate cautiously because inflation has slowed significantly from its peak two years ago and the economy remains sturdy. A separate report on Wednesday said health care, finance and other businesses in the U.S. services sector are continuing to grow, but not by as much as before and not by as much as economists expected. One respondent from the construction industry told the survey from the Institute for Supply Management that the Fed’s rate cuts have not pulled down mortgage rates as much as hoped yet. Plus “the unknown effect of tariffs clouds the future.” In the bond market, the yield on the 10-year Treasury fell to 4.18% from 4.23% late Tuesday. On Wall Street, Campbell’s fell 6% for one of the S&P 500’s sharper losses despite increasing its dividend and reporting a stronger profit for the latest quarter than analysts expected. Its revenue fell short of Wall Street’s expectations, and the National Football League’s Washington Commanders hired Campbell’s CEO Mark Clouse as its team president. Campbell’s said Mick Beekhuizen, its president of meals and beverages, will become its 15th CEO following Clouse’s departure. Gains for airline stocks helped offset that drop after JetBlue Airways said it saw stronger bookings for travel in November and December following the presidential election. It said it’s also benefiting from lower fuel prices, as well as lower costs due to improved on-time performance. JetBlue jumped 8.3%, while Southwest Airlines climbed 2.8%. In stock markets abroad, South Korea’s Kospi sank 1.4% following a night full of drama in Seoul. President Yoon Suk Yeol was facing possible impeachment after he suddenly declared martial law on Tuesday night, prompting troops to surround the parliament. Yoon accused pro-North Korean forces of plotting to overthrow one of the world’s most vibrant democracies. The martial law declaration was revoked about six hours later. Samsung Electronics fell 0.9% in Seoul. The country’s financial regulator said it was prepared to deploy 10 trillion won ($7.07 billion) into a stock market stabilization fund at any time, the Yonhap news agency reported. In the crypto market , bitcoin climbed back above $97,000 after Trump said he would nominate Paul Atkins , a cryptocurrency advocate, to chair the Securities and Exchange Commission. AP Writers Matt Ott and Zimo Zhong contributed.

Gary Lineker makes 'sack' joke as BBC prepare to replace long-serving Match of the Day host

Many beaches along the central and northern stretches of the Peruvian coastline were closed to prevent risk to human life, local authorities said. Waves there submerged jetties and public squares, sending residents fleeing to higher ground, according to images on local media. In neighboring Ecuador, the National Secretariat for Risk Management said a body was recovered in the coastal city of Manta. "The Manta Fire Department reported that, at 6:00 am, the body of a missing person was found lifeless in the Barbasquillo sector," the agency announced on social media. Peru closed 91 of its 121 ports until January 1, the National Emergency Operations Center said on its X social media account. The municipality of Callao, close to the capital Lima and the location of the country's main port, closed several beaches and barred tourist and fishing boats from venturing out. "These waves are being generated thousands of kilometers away from Peru, off the coast of the United States," navy Captain Enrique Varea told Channel N television. "They are waves generated by a persistent wind on the surface of the ocean that is approaching our coasts," he said. Dozens of small fishing boats and businesses near the sea were affected, according to images broadcast on television and social networks. axl/rmb/nro/acb

Although Shenghua Wen entered the United States on a student visa, eventually settling in San Bernardino County, law enforcement officials say he had a more nefarious purpose: exporting shipments of firearms, ammunition and other military items to North Korea. Federal authorities on Tuesday arrested Wen, 41, at his Ontario home, alleging he acted as an operative for the North Korean government, smuggling illicit goods concealed inside shipping containers from Long Beach. Wen, who authorities said is a Chinese national living illegally in the U.S. after overstaying his visa, has been charged with conspiracy to violate the International Emergency Economic Powers Act, which deals with sanctions and frozen foreign assets. If convicted, he could face up to 20 years in prison. Wen’s federal public defender did not immediately respond to a request for comment. It is illegal to supply North Korea with certain technologies and military supplies without U.S. government approval, according to U.S. Atty. Martin Estrada. “North Korea engaged in a scheme to circumvent and evade those restrictions,” Estrada said at a news conference Tuesday morning. “It’s essential we keep sensitive materials, including military equipment, outside the hands of our adversaries where they can harm us or our allies.” Wen, who arrived in the U.S. in 2012, was “key to this scheme and central to this plot” by North Korea, Estrada said. Before leaving China, Wen met with North Korean officials at two consulates, where they allegedly directed him to procure goods in the U.S., according to a Nov. 26 criminal complaint. In an interview with federal authorities, Wen said he was probably chosen for this role because he was good at smuggling, according to prosecutors. Wen told authorities that while he was in the U.S., two North Koreans living in China, whom he identified as Jin Yong Nan and Cui, reached out to him. Wen kept in contact with Cui via an encrypted messaging platform, according to the complaint. In his interview with federal authorities, Wen allegedly admitted he shipped two containers of firearms and other items to North Korea via Hong Kong in October and December 2023. One shipment was labeled as a refrigerator, another as camera parts, Estrada said. Wen allegedly received money for the containers and shipping fees — totaling at least $2 million — from North Korean officials. To obtain the weapons, Wen paid $150,000 to buy Super Armory, a business with a federal firearms license that he later registered in Texas. Wen allegedly used the company and people known as straw purchasers to assemble shipments, according to the complaint. Authorities said he would then drive the guns and ammo from Texas to California. Federal authorities said they also found emails and text messages from January to April, between Wen and a U.S.-based broker about obtaining a civilian airplane engine. During a September interview with authorities, Wen said North Korean officials told him to purchase plane engines, which would be used to help develop the North Korean military drone program, according to the complaint. At Wen’s home on Aug. 14, law enforcement officials seized two devices that he allegedly intended to send to North Korea for military use: a chemical threat identification device and a handheld countersurveillance gadget that detects electronic eavesdropping, according to the complaint. On Sept. 6, law enforcement seized about 50,000 rounds of 9-millimeter ammunition — stored in his white Ford van — that he’d allegedly obtained to send to North Korea, authorities said. Wen told authorities he believed the North Korean government wanted the items he sent to prepare for an attack against South Korea, according to the complaint. Wen allegedly told authorities that the government wanted him to obtain military uniforms to be used by the North Korean military to disguise its soldiers during a surprise offensive. Wen’s student visa was valid from Dec. 5, 2012, to Dec. 3, 2013, according to the complaint. Estrada said it’s unclear whether that was legitimate and whether he was actually studying. Wen was ordered removed from the U.S. in 2018 and, after a 2021 arrest, he signed a form acknowledging his overstay status, according to the U.S. attorney’s office. It’s unclear how he was able to stay in the country. Estrada said authorities learned about Wen through multiple tips, including from some individuals from whom he tried to purchase items. “We can’t say how long he was operating this. The investigation continues,” Estrada said.Rainbow Warriors' Rally Falls Short in Phoenix, UH Basketball Succumbs to Grand Canyon University