July 23, 2024 | International, Security
November 30, 2018 | International,
Reinventing Drug Discovery and Development for Military Needs
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.
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June 14, 2018 | International, Aerospace
Despite some opposition, US on course to deliver F-35s to Turkey on June 21
WASHINGTON — The U.S. government is proceeding with plans to deliver the first F-35 to Turkey, with the country set to accept its first jet on June 21 despite opposition from some in Congress. A Lockheed Martin spokesman confirmed to Defense News that it's still gearing up for a rollout ceremony at its production facilities in Fort Worth next week. “The F-35 program traditionally hosts a ceremony to recognize every U.S. and international customer's first aircraft. The rollout ceremony for Turkey's first F-35 aircraft is scheduled for June 21,” the spokesman said in a written statement to Defense News. “The aircraft will then ferry to Luke Air Force Base, Arizona, where Turkish pilots will join the F-35A training pool.” The Senate is set to vote this week on the annual defense policy bill, which includes language that would prohibit the U.S. government from “transfer of title” to Turkey until the time that the Defense Department submits a report to Congress on removal of Turkey from the F-35 program. But even if that language succeeds in the Senate, the defense policy bill will proceed to conference, where a group of armed services committee members will hammer out differences between the House and Senate versions to emerge with a single, final piece of legislation. That process could take months. Congress's opposition to allowing Turkey to purchase the F-35 hovers around two points: the country's detainment of American pastor Andrew Brunson and a deal to purchase the Russian S-400 air defense system. But for now, it appears that the Defense Department has no plans to keep Turkey from getting its first F-35 or to put restrictions on its use at Luke AFB. Thomas Goffus, the Defense Department's deputy assistant secretary of defense for Europe and NATO, acknowledged during an Atlantic Council event Wednesday that Turkey's acquistion of the S-400 could present the U.S. military and NATO alliance with added technical risks. But he would not go as far to spell out what actions the Defense Department is considering or could consider later down the road — perhaps a sign that the Pentagon is waiting to see how this legislation shakes out. “We have a process to evaluate the risks to Western technology that that [procurement] would present. Our preference is that they do not acquire the S-400,” Goffus said. “Given that, they are a sovereign nation, and they are trying to take care of their defense needs,” he added. “What restrictions are placed on them and what Congress will eventually pass, I can't even speculate on it on this point.” By the time Congress passes legislation that could curb Anakara's F-35 ownership, the country will likely have already started building up its first squadron at Luke AFB. There, Turkish pilots and maintainers will train alongside U.S. ones, moving from academic courseware to live flights. NATO and U.S. Defense Department officials have warned Turkey that if it continues down the path of purchasing the S-400, it will not be able to plug it in with NATO technologies like the F-35. SASC, in its policy bill, echoed those concerns, saying that Turkey's purchase of Russian hardware would “degrade the general security of the NATO alliance [...] and degrade interoperability of the alliance.” After a meeting in Washington with U.S. Secretary of State Mike Pompeo earlier this month, Turkish Foreign Minister Mevlüt Çavuşoğlu expressed confidence that the United States would not only deliver the first F-35 to Turkey as planned, but that it would ultimately decide to continue F-35 sales to Turkey. “Turkey rejects threatening language from the U.S. on the issue, it is not constructive,” Çavuşoğlu said on June 4, according to a report from the Turkish newsgroup Anadolu Agency. Turkey plans to buy 100 F-35As. As a partner of the program, its domestic defense industry helps build the Joint Strike Fighter. Most notably, Turkish Aerospace Industries' serves as a manufacturer of the aircraft's center fuselage. It has also been chosen as a sustainment hub for the international F-35 community. https://www.defensenews.com/smr/nato-priorities/2018/06/13/despite-some-opposition-us-on-course-to-deliver-f-35s-to-turkey-on-june-21/
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September 24, 2018 | International, Aerospace, C4ISR
Here’s how Air Mobility Command will improve aircraft survivability
By: Charlsy Panzino In a great power conflict, mobility aircraft will be essential to deliver fuel and supplies to the warfighters. But increasing concern over anti-access/area denial threats from potential foes, and the fact that big bodied mobility aircraft present inviting, in fact, critical targets has the attention and concern of Air Force leadership. The new head of Air Mobility Command is focusing on four key areas to improve the survivability of mobility aircraft and gain persistence over the battlefield. Gen. Maryanne Miller, who took the controls Sept. 7 when Gen. Carlton Everhart retired, told reporters at the Air Force Association's annual Air, Space and Cyber Conference that the Illinois-based command is looking at four categories of survivability improvements: Situational awareness of the battlefield New countermeasures to operate in a combat environment Self-defense systems Disciplined signature management “Looking at each one of these categories will help advance the survivability for our platforms in the threat environment,” Miller said Tuesday. Miller is carrying forward work that was done under her predecessor. Early this year, AMC completed an assessment about how to improve the survivability of aircraft in contested environments. The “High Value Airborne Asset” study recommended improvements to communications, situational awareness and self-protection systems. There are many different technologies to consider and develop for self-protection. including light armor, signature management tech and high-energy lasers. Former AMC commander Gen. Carlton Everhart often talked about his desire to put lasers on mobility aircraft, beginning with the KC-135, and the command has also been working to improve secure communications, notably on the C-17. The service needs integrated situational awareness capabilities that provide all aspects of pertinent battlefield information. New sensors will help the command better understand everything that's happening within the battlefield. As Air Mobility Command looks at how best to build that situational awareness, it could mean building sensors onto the aircraft or new air frames to meet those requirements. “Given the threat environment, it's probably a little bit of both,” Miller said. With signature management, or detection avoidance, Miller said AMC is looking at new air frames that will have common cockpits, advanced propulsion systems, payload, offload, range, speed and fuel efficiency. Miller said the command is figuring out if modifications can be made on current air frames or if new ones need to be built. “We're really trying to take advantage of signature management properties associated with each air frame itself,” she said. Meanwhile, U.S. Transportation Command and the Cost Assessment and Program Evaluation organization within the Office of the Secretary of Defense have been assessing the number of tanker aircraft, airlift aircraft and sealift ships needed to meet future combatant commander requirements. The study, known as the Mobility Capabilities and Requirements Study, is expected to be completed this fall. “America's air refueling fleet is the most stressed of our air mobility forces," Gen. Darren McDew, commander of USTRANSCOM, told the House Armed Services Committee earlier this year. “The combination of an aging fleet, increasing demand, and global tanker distribution puts a significant strain on this scarce national resource.” “Our ability to deploy decisive force is foundational to the National Defense Strategy. The size and lethality of the force is of little consequence if we can't get it where it needs to go when we want it there,” said McDew. The rate of change in technology requires quick innovation to overcome threats, Miller said. The force needs aircraft that are “able to survive, integrate and operate in DoD forces in current and future threat environments.” Miller said the key is understanding the threats of the future and modifying or building a plane that allows the Air Force to operate through that threat environment. https://www.airforcetimes.com/news/your-air-force/2018/09/22/heres-how-air-mobility-command-will-improve-aircraft-survivability