November 30, 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.
January 17, 2023 | International, Naval
The U.S. Navy and its closest allies and partners continue their quest to become interchangeable, but they canât do it without international supply chains.
October 1, 2018 | International, Aerospace
By: Valerie Insinna WASHINGTON — Boeing is the biggest aircraft manufacturer in the world, but the losses of the joint strike fighter program and Air Force's long range strike bomber still weigh heavily on the company's defense unit, and had prompted some in industry to wonder if the company's days of making cutting edge combat aircraft were numbered. Conventional wisdom held that Boeing needed to win either the Navy's unmanned tanker drone or the Air Force's next-generation trainer aircraft contract to keep its St. Louis, Mo.-based facility building tactical aircraft into the 2030s. a contract for the Air Force's Huey replacement helicopter was seen as out of reach as the service had formerly expressed a preference for sole-sourcing Black Hawks. But in a matter of weeks, Boeing racked up all three contracts, shocking the defense establishment. First came the MQ-25 Stingray award for the Navy's unmanned tanker drone on Aug. 30. An initial $805 million contract covers the design, development, fabrication, test and delivery of four Stingray drones, but Navy acquisition boss James Geurts said the entire program could be worth up to $13 billion for 72 aircraft. “It is a big win on a high-visibility competition/program and gives Boeing a franchise unmanned program,” wrote Roman Schweizer of Cowen Washington Research Group on Sept. 4. Boeing defeated Lockheed Martin and General Atomics to win the program — and that victory allows Boeing to cement its own status as the Navy's premier manufacturer of fixed-wing aircraft. “A Lockheed Martin win would have cemented its position as the builder of ‘next-gen' naval aviation platforms while Boeing would have been relegated to manufacturing fleet workhorses,” Schweizer said in his assessment of the award. “General Atomics would have a been a one-off, but we thought they would been a favorite for a low-cost, low-risk design.” Then on Monday, Boeing won another big competition — this time worth up to $2.38 billion — for the Air Force's UH-1N replacement helicopter. Boeing and Leonardo were immediately obligated $375 million for the initial four MH-139 helicopters, which will be built at Leonardo's commercial AW-139 production plant in Philadelphia. It was huge news for Leonardo, a large Italian defense contractor that had been attempting to break into the U.S. market with a major program for about a decade. But for Boeing, it was still a relatively small aircraft procurement program, with Byron Callan, an analyst with Capital Alpha Partners, writing that there were probably few opportunities for Boeing-Leonardo to sell the MH-139 to other users in the U.S. military. However, Boeing on Thursday won the major opportunity it had been seeking: the Air Force's T-X program. Boeing's clean sheet design beat out Lockheed and Leonardo to win a contract worth up to $9.2 billion. It's likely the actual program will be worth considerably less — Boeing would be obligated a total of $9.2 billion over time if the Air Force decides to execute all options on the contract for 475 training jets, and the services' program of record sits at 350 jets. But its importance to Boeing extends past the award's total contract value. Winning T-X was “possibly critical” for Boeing's St. Louis plant and for its defense business to remain a competitive player in tactical aircraft design, said Callan. “The MQ-25 win helps sustain production at that facility, which now builds F/A-18s and F-15s,” he wrote after the Sept. 27 announcement. “However, the F/A-18 and F-15 lines may end by the mid-2020s. T-X enables Boeing to keep that facility humming and therefore in the hunt for Penetrating Counter Air and other new military aircraft programs.” Analysts like Callan and Schweizer had speculated that Boeing would bid very aggressively to try to win the contract, but the question was whether the company could possibly offer a new purpose-built design at a significantly lower price point than competitors Lockheed Martin and Leonardo, which both proposed aircraft designs already in production and use by foreign militaries. It appears Boeing may have been able to do just that. Richard Aboulafia told Defense News in 2017 that the Lockheed and Leonardo trainers came with a price tag of about $25 million, although both companies were expected to bid lower than that to be competitive. Meanwhile, Jim McAleese of McAleese & Associates pegged the unit cost of Boeing's T-X at an “eye-watering” $19 million, far below the Air Force's $45 million per plane expectation. That low price “establishes an extremely high burden for disappointed offerors of Lockheed or Leonardo” to launch a successful protest with the Government Accountability Office, he stated in a Sept. 28 email, although Lockheed and Leonardo could potentially argue that the Air Force's cost and schedule risk assessments are too optimistic, given that Boeing offered a new airframe. Callan also pointed out that the MQ-25 and T-X wins could be advantageous to Boeing's commercial business. In the past, the defense sector has developed new materials that have later been adapted for use by the airline industry. With Boeing acquiring autonomy-focused businesses like Liquid Robotics and Aurora while investing in startups through its HorizonX organization, it is possible advances in military unmanned tech could give way to autonomous commercial cargo planes or other future concepts. https://www.defensenews.com/industry/2018/09/28/boeings-big-month-capped-off-with-hat-trick-of-new-contracts
December 23, 2022 | International, Aerospace
The Pentagon plans to spend about $100 billion in the next five years to modernize its tactical aviation fleets.