Dieser Artikel ist mega interessant u. Evotec spielt eine zentrale Rolle!!! Artikel ist zwar lang, Evotec taucht aber immer wieder auf!!
COVID R&D: Pharmas align behind crowdsourcing solution
BioCentury is providing this story for free given the urgent need for information about the COVID-19 crisis. For more analysis, sign up for our daily email
By C. Simone Fishburn, Editor in Chief | Apr 16, 2020 | 5:41 AM CEST
Within under a month, a group that started as a mash-up of research heads has morphed into an organized and streamlined collaboration among top pharmaceutical company R&D leaders. Its simple name: COVID R&D. Its goal: To push forward therapies and vaccines against COVID-19 at breakneck speed.
As part of its service to the biomedical community, BioCentury has coordinated with the consortium to collate publicly available information on molecules under investigation for COVID-19. More than 250 therapies and vaccines are listed in BioCentury’s open-access information portal for all researchers, with more being added daily (see BioCentury’s COVID-19 Resource Center).
From the outset, the pharma group’s mission has been to share data, find the molecules with the greatest rationale for advancement into clinical trials, and put them into studies designed to yield the most meaningful results fastest.
At a minimum, the group aims to use its collective expertise to triage and advance the best opportunities from the deluge of assets being put forward for studies by biotechs and academic researchers.
At the start, there was no formal structure. There were phone calls, emails and Zoom meetings. Those ad hoc discussions produced an organized structure with a central group that branches into satellite teams with a series of plans.
The core group has so far garnered 17 companies, including 14 pharmas, the research biotech Evotec SE (Xetra:EVT) and VCs 5AM and Versant Ventures.
The starting kernel came from Andy Plump, president of R&D at Takeda Pharmaceutical Co. Ltd. (Tokyo:4502; NYSE:TAK) and Rupert Vessey, president of R&D at Bristol Myers Squibb Co. (NYSE:BMY), who had linked up with Kush Parmar, managing partner of 5AM, and Jerel Davis, managing director of Versant. Each one found their network was offering drug candidates against COVID-19, proposing collaborations and asking for advice. The VCs’ portfolio companies stood ready to redirect their programs in the urgency of the moment. At the same time, concern was growing among pharma R&D heads about overlap and redundancy. Their solution was to band together in a precompetitive forum to evaluate ideas fast but rigorously, eschewing consideration of market potential. The consortium has coalesced into five working groups: clinical phase repurposing led by Vessey; preventive vaccines coordinated by Mathai Mammen, global head of R&D for the Janssen Pharmaceutical Cos. unit of Johnson & Johnson (NYSE:JNJ); novel antibodies led by Hal Barron, CSO and president of R&D at GlaxoSmithKline plc (LSE:GSK; NYSE:GSK); novel small molecule antivirals headed by Jay Bradner, president of Novartis Institutes for BioMedical Research (NIBR) -- the research arm of Novartis AG (NYSE:NVS; SIX:NOVN); and preclinical repurposing sponsored by Werner Lanthaler, CEO of Evotec. COVID R&D also contains two platform working groups, for data sharing and clinical trial acceleration, headed by Plump and Keith Gottesdiener, respectively. Gottesdiener, a veteran of Merck & Co. Inc. (NYSE:MRK), stepped down as president and CEO of Rhythm Pharmaceuticals Inc. (NASDAQ:RYTM) last quarter. Contributions from member companies range from assets to FTEs to leveraging connections to expedite the programs. Other pharmas, whose representatives are spread across the groups, include AbbVie Inc. (NYSE:ABBV); Allergan plc (NYSE:AGN); Amgen Inc. (NASDAQ:AMGN); AstraZeneca plc (LSE:AZN; NYSE:AZN); Bayer AG (Xetra:BAYN); Eisai Co. Ltd. (Tokyo:4523); Eli Lilly and Co. (NYSE:LLY); Gilead Sciences Inc. (NASDAQ:GILD); and Roche (SIX:ROG; OTCQX:RHHBY). The consortium remains open to new members. BioCentury is not a member; it became involved via data-sharing discussions with several of the early members. BioCentury is aggregating and structuring information in the public domain; it is not involved in the consortium’s selection of assets to investigate. Moreover, BioCentury Editors are independently making all decisions about the data and contents included in BioCentury’s COVID-19 Resource Center. This week, BioCentury has launched a gateway for biotechs and researchers to submit compounds to be included in the Resource Center (see “Research Gateway”). In the coming days, the Resource Center also may offer the option to direct compounds to the COVID R&D working groups for consideration by the consortium. Fast and furious The ever-changing face of the disease and unfolding biology mean the COVID R&D group wants to remain versatile, preparing it to cover different needs through the course of the pandemic, and after. The initial working principle is to think in terms of three phases. The most immediate focus is on marketed or late-stage compounds with a rationale for use in COVID-19, a good safety profile and sufficient clinical and/or commercial supply. The bulk of the activity now is focused here, because it’s critical to get molecules into well-designed trials. “The purpose of this is that it needs to be quick. Data are needed as fast as possible,” Vessey told BioCentury. His group already has prioritized an undisclosed number of molecules. Globally, drug developers already have more than 50 repurposed agents in trials due to read out before June 30, though many are small studies and only one third compare treatment to placebo or another therapy (see “The Dam is About to Break”). The consortium’s second phase considers earlier-stage repurposed assets with evidence for use in COVID-19, or other late-stage or marketed assets that could prove relevant as more is uncovered about the disease biology. The third involves novel assets developed to prevent or treat COVID-19. The consensus at this point is that joining or creating a master protocol would be the optimal means of testing multiple molecules in the clinic quickly and reliably. Master protocols allow molecules to be tested in different patient populations -- here, meaning patients at different stages of the disease course. This is an important factor in COVID-19 as the biology demands different mechanisms at different stages (see “Closing in on Matching Disease Mechanism to Disease Stage”). Gottesdiener told BioCentury that COVID R&D is talking with the organizers of the U.K.’s RECOVERY (Randomised Evaluation of COVID-19 Therapy) master protocol and the international REMAP-CAP (Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia), as well as with NIH, which is running the Adaptive COVID-19 Treatment Trial (ACTT) (see “Master Protocols Emerge as a Critical Clinical Tool”). In parallel, Elliott Levy, SVP global development at Amgen Inc., is leading the consortium’s initiative to design its own master protocol, also as part of the first wave. The later phase activities are equally important. While repurposed drugs represent the best chances in the near term to stem the pandemic, it’s highly unlikely that a single drug or vaccine will stop COVID-19 in its tracks, in particular one coming from a repurposed drug not designed specifically for SARS-CoV-2, the virus that causes the disease. The group is designing its work in anticipation of a potential second or even third wave of COVID-19. The parallel effort on vaccines addresses what J&J’s Mammen said would be the “definitive solution to this crisis.” The idea is to have “a network set up and protocols ready” for companies with innovative products to employ, said Gottesdiener. “We are not only building for today, but to create a strategic framework for when a third wave comes,” regardless of what the consortium’s own structure looks like by then, he said. Ideas abound Asset ideas can arise from the consortium companies’ own pipelines, biotechs, academic groups or other organizations. There is no transfer of IP associated with COVID R&D, according to the participants. Companies submitting assets to the effort will retain the IP they own, allowing it to be licensed in subsequent partnerships. An overarching principle among all the consortium’s groups is to prioritize molecules or mechanisms that are not being adequately tested by individual companies or other consortia. One consideration is whether a compound can be rapidly scaled for manufacturing. Without that capability, the potential short-term utility would be low, meaning such compounds would be unlikely to make the first wave. Barron’s group, which includes Mene Pangalos, EVP of biopharmaceuticals R&D at AZ, is evaluating novel antibody opportunities. Specifically, Barron said the team is looking for clues to how the body generates neutralizing antibodies by studying patients who have been infected with coronavirus and successfully recovered. “By further optimizing these antibodies we should be able to create an effective therapy for infected patients or even to prevent illness in those at risk for developing the infection,” Barron told BioCentury. The preclinical working group is responsible for defining assays and a strategy that provides a unified platform for comparing candidates. As head of the small molecule antiviral group, Bradner is deploying his NIBR team to use these and other assays to understand of the structure-function of viral proteins for the project, building on knowledge from earlier outbreaks. “Insights guiding target selection in the SARS-CoV-2 genome are well supported by analogy to prior research on MERS and SARS, which serve as a chilling reminder of the need for direct anti-coronavirus therapeutics,” Bradner told BioCentury. He said NIBR has initiated “definitive therapeutic discovery” on the main protease (Mpro), owing to its apparent essentiality and druggability. Bradner added: “We have taken an open science approach, inviting insights from the community in real time, so as to accelerate the program immediately, and importantly to sustain this research even after the COVID-19 pandemic wanes.” The preclinical repurposing group sponsored by Evotec’s Lanthaler will channel candidate molecules from consortium members or submitted from external groups to COVID R&D. “Where speed and quality are essential, access to unbiased systematic and efficient screening and preclinical platforms in all modalities for biotech, pharma and academia, is paramount,” Lanthaler told BioCentury. Evotec EVP of Infectious Diseases Kara Carter, who runs the team, told BioCentury the initial screening assays will assess whether compounds have activity against SARS-CoV-2, using single concentrations first for molecules without sufficient human data, and then dose-responses for all molecules to determine potencies. “Once we have identified potent compounds, the individual contributors will decide if they want to keep their compounds in the work stream for prioritization and assessment or take their own path to find a partner or fill in missing data,” said Carter. For compounds that remain in the work stream, she said triaging is important because downstream assays, such as infection of primary human airway epithelia and preclinical pharmacology models, are low throughput. “The goal is to identify at least one compound that can be moved to clinical development and to do that in the fastest way possible based on quality data,” Carter said.
Open Era Data sharing represents a core tenet in COVID R&D. Anne Heatherington, Takeda SVP and head of data sciences, leads the aggregation of data from multiple sources including BioCentury, and integration of those data to support evaluation of molecules and design of trials. In particular, the data group is focused on individual patient data, so that it can form a better data-driven understanding of the natural history of the disease, standard of care treatment and population subsets, and what clinical data are routinely collected. To that end, the consortium is open to working with anyone in the context of patient-level data and natural history. Like Carter, Plump noted the consortium is using a flexible model that allows members to advance their own portfolio compounds independently or via COVID R&D. “The principle is that these aren’t meant to be mutually exclusive activities; they’re meant to be enabling activities. Companies can do their own thing as they want. But the more we can share information and learn from one another, the better this will be,” Plump told BioCentury. 5AM’s Parmar and Versant’s Davis expect biotechs will benefit. “By sharing the latest information, research and development capabilities, and access to global basket trials, the consortium provides a unique resource,” said Davis. Parmar said COVID R&D offers “unprecedented access to top R&D leaders” for small companies rallying to contribute. “The idea is for the dialogue to happen outside of any ‘classical’ BD kind of process -- this is about trying to qualify the most credible efforts and support them with the best possible expertise, openly collaborate with them, or at least point them in the right direction to advance,” he said. CONSORTIUM MEMBERS Hal Barron, CSO and president of R&D, GlaxoSmithKline plc Jay Bradner, president of NIBR, Novartis AG Joe Berryhill, global alliance director, Roche Kara Carter, EVP of infectious diseases, Evotec SE Christopher Corsico, SVP and head of development, GlaxoSmithKline plc Jerel Davis, managing director, Versant Ventures Keith Gottesdiener, independent (former CEO, Rhythm Pharmaceuticals) Anne Heatherington, SVP and head of data sciences institute, Takeda Pharmaceutical Co. Ltd. Thomas Hudson, SVP of R&D and CSO, AbbVie Inc. Lynn Kramer, corporate officer, Eisai Co. Ltd. Werner Lanthaler, CEO, Evotec SE Rob Lenz, VP, neuroscience, inflammation, nephrology and head of center for design and analysis, Amgen Inc. Elliott Levy, SVP global development, Amgen Inc. Mathai Mammen, global head of R&D for Johnson & Johnson’s Janssen Pharmaceutical Cos. Joerg Moeller, EVP and head of R&D, Bayer AG David Nicholson, EVP & chief R&D officer, Allergan plc Mene Pangalos, EVP of biopharmaceuticals R&D, AstraZeneca plc William Pao, head of pharma research and early development (pRED), Roche Kush Parmar, managing partner, 5AM Ventures Merdad Parsey, EVP and CMO, Gilead Sciences Inc. Peter Pertel, global head of translational medicine, respiratory and infectious diseases, NIBR, Novartis AG Andy Plump, president of R&D, Takeda Pharmaceutical Co. Ltd. David Reese, EVP R&D, Amgen Inc. Carlo Rizzuto, partner, Versant Ventures Daniel Skovronsky, president of Lilly Research Labs and SVP science and technology, Eli Lilly and Co. John Tsai, head of global drug development and CMO, Novartis AG Rupert Vessey, president of research and early development, Bristol Myers Squibb Co. Within under a month, a group that started as a mash-up of research heads has morphed into an organized and streamlined collaboration among top pharmaceutical company R&D leaders. |
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