30 novembre 2018 | International,
Flying at 50,000 feet, diving deep in the ocean, or hiking for miles with gear through extreme climates, military service members face conditions that place unique burdens on their individual physiology. The potential exists to develop pharmacological interventions to help service members complete their toughest missions more safely and efficiently, and then recover more quickly and without adverse effects, but those interventions must work on complex physiological systems in the human body. They will not be realized under the prevailing system of drug discovery and development with its focus on engaging single molecular targets. DARPA created the Panacea program to pursue the means of rapidly discovering, designing, and validating new, multi-target drugs that work with the body's complexity to better support the physiological resilience and recovery of military service members.
The premise of Panacea is that the physiological systems of the human body work in complex and highly integrated ways. Drugs exert effects on our bodies by physically interacting with and changing the functional state of biomolecules that govern the functions of cells and tissues. Most drugs target proteins, which are the principle cellular workhorses. Ideally, drugs would target multiple proteins simultaneously to exert precise, network-level effects.
One major problem facing the drug development community is that the functional proteome — the complete collection of proteins and their roles in signaling networks — is largely dark to science. Despite being able to identify many of the proteins within a cell, researchers do not have a firm grasp on everything those proteins do and how they interact to affect physiology.
Due to this sparsity of structural and functional knowledge, the state of the art in drug development — what Panacea seeks to transform — is to engage only a very small fraction of known protein targets to achieve an effect. In fact, today's approach to drug design singles out individual proteins in certain cells. That hyper-specificity is an attempt to minimize the risk of side effects and speed time to market, but it also yields a thin stream of drugs, many of which have similar mechanisms and relatively muted effectiveness compared to what might be achieved using a multi-target, systems-based approach.
“The current roster of drugs approved by the U.S. Food and Drug Administration only targets about 549 proteins, yet the body can produce more than six million different protein variants,” said Tristan McClure-Begley, the Panacea program manager. “The opportunity space for pharmacological intervention is vast and effectively untapped, but to access it we need new technology for understanding and targeting the human functional proteome.”
Panacea will address the lack of functional knowledge about the proteome. DARPA's call to the research community is to consider complex physiological conditions relevant to military service members — for instance, metabolic stress during extreme endurance missions or pain and inflammation after injury; investigate the molecular mechanisms underlying those conditions; identify multiple, key molecular targets involved; and develop novel medicinal chemistry approaches to synthesize interventions that modulate those targets. DARPA believes that multi-target drugs will deliver safer and more efficacious solutions to military requirements for readiness and recovery over state-of-the-art interventions.
“Many of the most successful drugs produced in the past were found rather than made, and we knew what they did long before we knew how they did it,” McClure-Begley said. “To deliver improved interventions, we need to get to a place where we can investigate all of the potential proteins at play for a given condition and then prioritize sets of protein targets and signaling networks to effectively modulate physiological systems, regardless of what prior knowledge exists about those targets.”
The Panacea program aims to generate initial proof of concept for this new direction in drug discovery and development. Research will primarily involve animal models, human cell derived organoids, and high-throughput cell culture models. However, to support eventual transition to humans, DARPA will work with federal agencies to develop a regulatory pathway for future medical use. By the end of the five-year program, DARPA will require teams to submit novel drug candidates to the U.S. Food and Drug Administration for review as an Investigational New Drug or for Compassionate Use.
DARPA will hold a Proposers Day on December 14, 2018, in Arlington, Virginia, to provide more information about Panacea and answer questions from potential proposers. For details of the event, including registration requirements, visit https://go.usa.gov/xP6hD.
A forthcoming Broad Agency Announcement will fully describe the program structure and objectives.
12 septembre 2022 | International, Aérospatial, Naval, Terrestre, C4ISR, Sécurité
The Defense Innovation Unit is seeking commercial software to support new supply chain pathways and manage risk across the industrial base.
2 juin 2022 | International, Aérospatial, Naval, Terrestre, C4ISR, Sécurité
Appelés au vote le 1er juin, une large majorité de citoyens du Danemark, presque 67%, ont mis fin à l'exemption qui les dispensait de contribuer à la politique de sécurité et de Défense commune (PSCD) de l'Union européenne. Il s'agira donc de la fin d'un régime d'exception qui durait depuis plus de 30 ans, à la suite du rejet massif du traité de Maastricht, en 1992. « Le Danemark a envoyé un signal important à nos alliés en Europe et l'Otan » a déclaré la Première ministre social-démocrate Mette Frederiksen. Elle était parvenue à un accord en mars dernier avec cinq partis de droite et de gauche pour mettre sur pied ce référendum, ainsi que pour augmenter les dépenses de Défense de 1,4% à 2% du PIB d'ici à 2033. Ursula von der Leyen, la Présidente de la Commission européenne, a quant à elle, salué le message fort d'engagement envers la sécurité commune envoyé par le peuple danois. Les Echos du 2 juin
26 février 2020 | International, Aérospatial
By Matthew Cox WEST PALM BEACH, Florida -- Sen. Tammy Duckworth, a former U.S. Army helicopter pilot, said recently that the Marine Corps, Navy and Air Force would have to wait their turn if they want their own version of the Army's futuristic helicopters being developed under the Future Vertical Lift (FVL) effort. The Illinois Democrat and member of the Senate Armed Services Committee recently attended a high-profile flight demonstration of Sikorsky-Boeing's new SB-1 Defiant helicopter that was designed with the goal of replacing the UH-60 Black Hawk. The Army awarded a team from Sikorsky, part of Lockheed Martin Corp., and Boeing Co. a 2014 contract to build Defiant as part of the Joint Multi Role Technology Demonstrator (JMRT-D) program. A Textron Inc.-Bell team also received a contract under the effort and built the V-280 Valor, a tiltrotor-design helicopter that completed its first test flight in December 2017. Both the Valor and the Defiant prototypes are promising designs, Army officials maintain, that are capable of flying at speeds of more than 200 knots and will result in a replacement for the venerable Black Hawk as the service's new Future Long Range Assault Aircraft (FLRAA). Duckworth, a former Army National Guard officer who lost both legs after enemy forces shot down the Black Hawk she was flying over Iraq in 2004, said she intends to keep the FVL program from morphing into an unwieldy, joint effort. That's a pitfall that has thrust many joint-service programs into program delays and cost-overruns because of overly broad requirements. "This is an Army aircraft; we need to keep an Army mission," Duckworth told reporters at the Feb. 20 flight demo. "If the other services want to fall in behind it and develop something afterward and tweak it for what they need, that is fine, but we cannot build a Frankenaircraft ... that's going to meet the Marines' needs and the Navy's need and the Air Force's needs. "We need to not let the requirements start to meander and creep around because otherwise we will never get to where we need to and get these things fielded as quickly as possible," she added. In the past, the Pentagon has often tried to develop multiple versions of a major combat system, such as the new F-35 Joint Strike Fighter, which has been designed to satisfy the requirements of the Navy, Marine Corps and Air Force. The acquisition program for the advanced, stealth fighter began in the mid-1990s and still suffers from testing setbacks that have delayed a full-rate production decision. That Army-Marine Corps Joint Light Tactical Vehicle (JLTV) program, however, is considered a successful acquisition effort that began in 2006 after Humvees in Iraq could not withstand the destruction force of enemy homemade bombs attacks. JLTV took almost a decade to become a reality but, in August 2015, Oshkosh Corp. was selected over Lockheed Martin Corp. and AM General LLC to build the vehicle for the Army and Marine Corps. Meanwhile, for the second year in a row, the Army has reduced the number of JLTVs it will buy in fiscal 2021 to free up money to fund future modernization. FVL is one of the Army's top modernization priorities under a new strategy the service launched in 2017, with the goal of replacing most of its major combat platforms beginning in 2028. Leaders stood up Army Future Command, an organization designed to help the service's acquisition and requirements machines work more closely together in an effort to streamline what has traditionally been a slow-moving process to develop and field combat system. So far, the strategy appears to be working, since the FLRAA and the Future Attack Reconnaissance Aircraft (FARA) efforts are ahead of schedule, Duckworth said. Army officials are scheduled to down-select to two vendors to build final prototypes of the FARA next month. The service is also scheduled to begin a competitive demonstration and risk reduction phase for FLRAA, which is expected to last until 2022, the year the service plans to down-select to one vendor to build the Black Hawk replacement. "This is rare for defense procurement to actually be ahead of timeline instead of pushing everything to the right," Duckworth said. "I am very pleased with how well the Army is handling this development." The senator stressed, however, that she intends to continue strict oversight of the FVL to ensure it doesn't result in a waste of taxpayer dollars. "We can't be spending upward of $60 million per airframe," Duckworth said. "If we do that, then we can't field the number of airframes that we need to be out there in the force." Army Secretary Ryan McCarthy, who also attended the flight demo, stressed that the service's leadership is committed to making necessary cuts to outdated programs to free up money for FVL and other modernization efforts. "We don't have a choice. We are running out of letters to upgrade the existing platforms -- they are 40-year-old systems; the technology will not endure," he said. -- Matthew Cox can be reached at matthew.cox@military.com. https://www.military.com/daily-news/2020/02/25/duckworth-armys-new-helicopters-should-not-be-designed-anyone-else.html