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Thursday, December 31, 2020

Codiak Reports Positive Initial Phase 1 Results

– exoIL-12 resulted in no local or systemic treatment-related adverse events –

– Local administration of exoIL-12 demonstrated no systemic exposure to IL-12 –

– Dose selection data and advancement into multi-dose study in cutaneous T cell lymphoma patients anticipated in Q1 2021 –

Codiak BioSciences, Inc. (NASDAQ: CDAK), a clinical-stage biopharmaceutical company focused on pioneering the development of exosome-based therapeutics as a new class of medicines, today announced that the primary objectives were met in the initial part of its Phase 1 trial, which evaluated a single ascending dose of exoIL-12 in healthy volunteers. In this randomized, placebo controlled, double-blind study, exoIL-12 demonstrated a favorable safety and tolerability profile, with no local or systemic treatment-related adverse events and no detectable systemic exposure of IL-12.

“This is an important milestone, as these results show that exoIL-12 acts in humans as we had expected, based on our preclinical evaluations. The safety and tolerability profile observed here support the target profile that we are hoping to achieve with this candidate,” said Benny Sorensen, M.D., Ph.D., Senior Vice President and Head of Clinical Development, Codiak. “We’re looking forward to advancing exoIL-12 into the multi-dose part of the study in cutaneous T cell lymphoma patients and presenting the detailed results from the healthy volunteer part of this study at an upcoming medical conference.”

exoIL-12 is the first engineered exosome therapeutic candidate to be evaluated in humans and one of two Codiak programs currently in clinical development. exoIL-12 was engineered using the company’s proprietary engEx™ Platform and designed to display functional IL-12 on the exosome surface using the exosomal protein, PTGFRN, as a scaffold, the capability of which was identified by Codiak scientists.

IL-12 is a potent anti-tumor cytokine, but prior clinical development conducted by others1 of recombinant IL-12 (rIL-12)-based therapies has generally been hindered by significant safety and tolerability concerns. To overcome these limitations, exoIL-12 was designed to facilitate dose control of IL-12 and limit systemic exposure and associated toxicity by localizing IL-12 in the tumor microenvironment (TME) in order to potentially expand the therapeutic index.

Q&A on new coronavirus variant with Fred Hutch scientist tracking it

 With the U.S. on Tuesday recording its first known case of the novel coronavirus variant that’s been sweeping across the U.K., the pressure is on to track the variant’s spread and parse out why it seems to be more contagious — and what that means for the future of the pandemic.

At the center of those efforts is a group at the Seattle-based Fred Hutchinson Cancer Research Center that has been cataloging and analyzing genetic changes in the virus since the pandemic began. Nextstrain, co-founded by Hutch computational biologist Trevor Bedford, is an uber-dashboard of genomics, mapping out mutations and the routes followed by every known variation of the virus so far.

Now, Bedford and the project’s far-flung team of bioinformatics experts are helping figure out how widespread the variant might already be in the U.S. and how quickly it could become dominant here, as it did in the U.K.

On Tuesday, Bedford answered questions about the new variant, including its potential impacts on vaccine effectiveness and development of herd immunity and whether additional measures might be needed to keep it in check.

The conversation has been edited for clarity and brevity.

Q: Detecting and monitoring the new variant requires sequencing the genomes of viruses from large numbers of infected people. How is that being done in the U.S.?

A: The U.K. early on decided to have a consolidated national approach to doing this genomic surveillance. They were able to have a few big labs do a lot of testing and then share positive specimens with a handful of big sequencing labs. In the U.S., most of public health is really at the state level. So what’s happened is that there are a handful of public health labs that are doing a good job of sequencing viruses that are collected in their state and sharing that. But there isn’t really a national strategy.

The CDC has given grants to help support academic labs and states to do this work, but it’s a bit slower than it should be. Because this work is done at the state labs, issues of personnel and resources mean that the sequencing often doesn’t end up as the top priority.

Q: The U.S. ranks 43rd in the world in the percentage of positive cases that are sequenced, and you were recently quoted in a New York Times editorial that called for a major expansion. Is anything being done?

A: The U.S. has sequenced and shared over 50,000 virus genomes, more than any country in the world, except for the U.K. However, the turnaround times have not been great. There are thousands of viruses that were shared in the database in December, but a great many of those were from specimens collected back in March.

The CDC has plans to (start) receiving specimens from the state labs and then doing the sequencing more centrally and share the data. So there are plans to have thousands more genomes sequenced every month, but I don’t know when that will come online.

Q: The first U.S. infection with the U.K. variant was reported Tuesday in a Colorado man in his 20s with no recent travel history. How prevalent do you think that variant and a similar one detected in South Africa are in the U. S.?

A: My working hypothesis is that they are here but circulating at very low levels. And if they are more transmissible, which I think is likely, then they will be expanding, and we’ll catch them when they hit some frequency threshold.Q: Travelers from the U.K. now need a negative coronavirus test to enter the U.S. How effective do you think that will be in slowing the spread of the variant?

TB: I think it’s smart at this point. I don’t have hope that we will be able to contain the U.K. variant in the U.K. in the same way I didn’t have hope in February that we were going to contain COVID in China. But testing to reduce the number of infected individuals traveling can still slow things down.

I think it might stop mattering so much once these variants become more common here.

Q: You’ve said the new variant might be slightly less susceptible to vaccine-induced immunity, but that it isn’t different enough to completely foil existing vaccines. Why?

A: The main reason I think that is because there’s a particular mutation in the U.K. variant that removes two different (portions) of the spike protein, and that tucks in a bit of protein that was sticking out and was an antibody target. So it removes that target for antibodies.

And there was a study from a lab in Cambridge … where they took serum from people who had recovered from COVID and measured it against wild type virus and against viruses that have this deletion. And they saw that the antibodies of the recovered individuals neutralize the mutated virus significantly less than the wild type virus.

If I had to hazard a guess, I believe we could see a modest reduction, like from 95% vaccine effectiveness to 85% or so, but I don’t think it would really severely inhibit the vaccine.

Q: If this variant becomes common and lowers the overall effectiveness of the vaccines even slightly, what are the implications for the development of herd immunity?

A: I think we’ll still get there. It’s just going to be a bit more challenging.

https://www.seattletimes.com/seattle-news/health/a-qa-about-the-new-coronavirus-variant-with-the-fred-hutch-scientist-whos-been-tracking-its-spread

Drugmakers to hike prices for 2021 as pandemic, political pressure put revenues at risk

 Drugmakers including Pfizer Inc, Sanofi SA, and GlaxoSmithKline Plc plan to raise U.S. prices on more than 300 drugs in the United States on Jan. 1, according to drugmakers and data analyzed by healthcare research firm 3 Axis Advisors.

The hikes come as drugmakers are reeling from effects of the COVID-19 pandemic, which has reduced doctor visits and demand for some drugs. They are also fighting new drug price cutting rules from the Trump administration, which would reduce the industry’s profitability.

https://www.reuters.com/article/us-usa-healthcare-drugpricing-exclusive/exclusive-drugmakers-to-hike-prices-for-2021-as-pandemic-political-pressure-put-revenues-at-risk-idUSKBN2951Q2

Bionano’s Genome Mapping Platform 'Could Be a Game Changer'

 Momentum might be an elusive quality, yet it is also pretty easy to spot. Right now, it is clearly on BioNano Genomics’ (BNGO) side. In December, shares of the life sciences company have accumulated a mighty 328%.

Evidently, investors are buying into the cytogenetics specialist’s steady stream of positive developments.

On Monday, the company disclosed that its genome mapping platform Saphyr has been accredited in the US by the College of American Pathologists. The platform will be used by Bionano’s customer Praxis Genomics, marking it as the first company to offer a laboratory developed test (LDT) utilizing whole genome analysis.

Saphyr’s optical genome mapping is an alternative to traditional cytogenetic methods and Maxim analyst Jason McCarthy thinks it could be a game changer.

“Digital cytogenetics is one of the areas where Saphyr has the potential to change the clinical diagnostic landscape,” the 5-star analyst said. “Current methods are labor and time intensive, and therefore costly. Saphyr offers a more efficient and streamlined alternative as well as potentially improved diagnostic yield. As more LDTs are developed, we anticipate that adoption for Saphyr should increase, driving revenue for Bionano.”

While the accreditation is the first of its kind in the U.S., in Europe, whole genome clinical tests are already in progress across several applications including inherited genetic disorders and leukemia.

The news followed the recent publication of an article which further highlighted Saphyr’s qualities. In a comparison test, PacBio’s HiFi chemistry was only able to detect 72% of the large SVs (structural variants) detected by Saphyr.

All in all, McCarthy reiterated a Buy rating on BNGO shares along with a $2 price target. Due to Bionano’s latest surge, the figure indicates a 5% downside from current levels.

https://finance.yahoo.com/news/bionano-genome-mapping-platform-could-235053495.html 

North American deer mice are susceptible to SARS-CoV-2

 Bryan D. Griffin, Mable Chan, Nikesh Tailor, Emelissa J. Mendoza, Anders Leung, Bryce M. Warner, Ana T. Duggan, Estella Moffat, Shihua He, Lauren Garnett, Kaylie N. Tran, Logan Banadyga, Alixandra Albietz, Kevin Tierney, Jonathan Audet, Alexander Bello, Robert Vendramelli, Amrit S. Boese, Lisa Fernando, L. Robbin Lindsay, Claire M. Jardine, Heidi Wood, Guillaume Poliquin, James E. Strong, Michael Drebot, David Safronetz, Carissa Embury-Hyatt, 

Darwyn Kobasa

Canadian healthcare providers can now practice in Michigan

 Michigan Gov. Gretchen Whitmer signed a bill this week to immediately permit reciprocity in licenses, registrations and certifications for Canadian healthcare professionals in Michigan.

Canadian healthcare professionals can apply for reciprocity as long as they meet the educational, examination and billing requirements of Michigan law. The allowance had been in effect for Canadian health professionals from 2002 until it was allowed to expire in 2012.

Before licensing, registering, or certifying an applicant, the Michigan board of medicine, nursing or other licensing body may require a personal interview to evaluate the applicant's qualifications.


The bill was one of more than 80 pieces of legislation the governor signed to go into immediate effect Dec. 29, according to mlive.com.

https://www.beckershospitalreview.com/hospital-physician-relationships/canadian-healthcare-providers-can-now-practice-in-michigan.html

China Clampdown On COVID-19 Origins: AP Journalists Tailed, Samples Seized

 As the World Health Organization and other China puppets struggle to assemble a 'natural origin' theory for COVID-19, the CCP has been going to great lengths to quash non-sanctioned investigations that may instead point to a lab escape from research facilities which made international headlines in 2015 for dangerous 'gain-of-function' research - by which they were manipulating coronaviruses to better infect humans.

'Batwoman' Shi Zhengli, known for bioengineering bat coronaviruses, was criticized over dangerous 'gain-of-function' experiments

And while mainstream news outlets spent the better part of 2019 flatly rejecting lab-origin evidence as 'debunked conspiracy theories' - which earned ZeroHedge a temporary Twitter ban and a plethora of social media warning labels and 'fact checks' (including one from a former Wuhan Lab workerthe same mainstream outlets are now finding China's suppression of COVID-19 origin theories suspicious.

As part of their investigation, AP interviewed dozens of Chinese and foreign scientists and officials, while also reviewing leaked emails, internal data, as well as documents from China's CDC and cabinet. And what did they find? "A pattern of government secrecy and top-down control that has been evident throughout the pandemic."

...for scientists and journalists, it has become a black hole of no information because of political sensitivity and secrecy.

A bat research team visiting recently managed to take samples but had them confiscated, two people familiar with the matter said. Specialists in coronaviruses have been ordered not to speak to the press. And a team of Associated Press journalists was tailed by plainclothes police in multiple cars who blocked access to roads and sites in late November.

More than a year since the first known person was infected with the coronavirus, an AP investigation shows the Chinese government is strictly controlling all research into its origins, clamping down on some while actively promoting fringe theories that it could have come from outside China. -Associated Press

Let's quickly review the world's easiest game of connect-the-dots:

  • Peng Zhou, Wuhan Institute of Virology's head of Bat Virus Infection and Immunization, was researching "the molecular mechanism that allows Ebola and SARS-associated coronaviruses to lie dormant for a long time without causing diseases," while a press release from his lab was titled "How bats carry viruses without getting sick."
  • Zhou's colleague, Shi Zhengli, has been involved in bioengineering bat coronaviruses - co-authoring a controversial 2015 paper which described the creation of a new virus by combining a coronavirus found in Chinese horseshoe bats with another that causes human-like severe acute respiratory syndrome (SARS) in mice.
  • In 2015, Nature magazine expressed concern over Zhengli's experiments with bat coronavirus. The same year, the US government suspended funding to the lab  due to their concern over risks of experimenting with bat coronavirus.
  • Meanwhile, the US State Department warned over safety standards at the Wuhan lab in a series of cables beginning in 2015, according to the Washington Post's Josh Rogin.
  • Add to that China's active suppression of lab-origin theories while their partners at the World Health Organization continue to hunt for some heretofore non-existent crossover species, and it doesn't take Matlock to figure out that the official narrative is severely flawed.

    The government is handing out hundreds of thousands of dollars in grants to scientists researching the virus’ origins in southern China and affiliated with the military, the AP has found. But it is monitoring their findings and mandating that the publication of any data or research must be approved by a new task force managed by China’s cabinet, under direct orders from President Xi Jinpingaccording to internal documents obtained by the AP. A rare leak from within the government, the dozens of pages of unpublished documents confirm what many have long suspected: The clampdown comes from the top.

    As a result, very little has been made public. Authorities are severely limiting information and impeding cooperation with international scientists-Associated Press

    "What did they find?" asks Duke University epidemiologist, Gregory Gray, who oversees a lab in China studying the transmission of infectious diseases from animals to people. "Maybe their data were not conclusive, or maybe they suppressed the data for some political reason. I don’t know … I wish I did."

    Scientists familiar with China's public health system say the CCP's standard operating procedure of information control and censorship apply to all aspects of COVID-19 research.

    "They only select people they can trust, those that they can control," said one public health expert who works regularly with China's CDC. "Military teams and others are working hard on this, but whether it gets published all depends on the outcome."

    According to the report, Beijing worries that investigations will also reveal that they were negligent in the spread of the virus.

    Some public health experts warn that China’s refusal to grant further access to international scientists has jeopardized the global collaboration that pinpointed the source of the SARS outbreak nearly two decades ago. Jonna Mazet, a founding executive director of the UC Davis One Health Institute, said the lack of collaboration between Chinese and U.S. scientists was “a disappointment” and the inability of American scientists to work in China “devastating.”

    There’s so much speculation around the origins of this virus,” Mazet said. “We need to step back...and let scientists get the real answer without the finger-pointing.” -Associated Press

    Steering the narrative

    Now that AP has caught up and corroborated what we've been reporting on ad nauseam - albeit via burning their own hand on the stove - they're also piecing together the enormous disinformation campaign employed by Beijing to try and control the narrative.

    After the initial batch of COVID-19 cases were traced to the Hunan Seafood market in Wuhan, authorities began collecting samples for analysis - finding that 33 out of 585 environmental samples tested positive for the virus.

    "This corona(virus) is very close to SARS," wrote Canadian microbiologist Gary Kobinger, a WHO adviser, according to internal China CDC data obtained by AP. "If we put aside an accident ... then I would look at the bats in these markets (sold and ‘wild’)."

    Then, "As the virus continued spreading rapidly into February, Chinese scientists published a burst of research papers on COVID-19. Then a paper by two Chinese scientists proposed without concrete evidence that the virus could have leaked from a Wuhan laboratory near the market. It was later taken down, but it raised the need for image control."

    Internal documents show that the state soon began requiring all coronavirus studies in China to be approved by high-level government officials — a policy that critics say paralyzed research efforts.

    A China CDC lab notice on Feb. 24 put in new approval processes for publication under “important instructions” from Chinese President Xi Jinping. Other notices ordered CDC staff not to share any data, specimens or other information related to the coronavirus with outside institutions or individuals.

    Then on March 2, Xi emphasized “coordination” on coronavirus research, state media reported.

    The next day, China’s cabinet, the State Council, centralized all COVID-19 publication under a special task forceThe notice, obtained by the AP and marked “not to be made public,” was far more sweeping in scope than the earlier CDC notices, applying to all universities, companies and medical and research institutions.

    The order said communication and publication of research had to be orchestrated like “a game of chess” under instructions from Xi, and propaganda and public opinion teams were to “guide publication.” It went on to warn that those who publish without permission, “causing serious adverse social impact, shall be held accountable.” -Associated Press

    "The regulations are very strict, and they don’t make any sense," said one former China DCD deputy director on condition of anonymity. "I think it’s political, because people overseas could find things being said there that might contradict what China says, so it’s all being controlled."

    And after thousands of samples were taken from the Hunan Seafood market, no findings were ever made public. Yet, on May 25, CDC chief Gao Fu finally broke the silence - telling China's Phoenix TV that no animal samples from the market had tested positive, ruling out the market as the likely source of the virus despite its link to the majority of new cases in the region.

    China’s government-controlled media used the theory to suggest the original outbreak in Wuhan could have started with seafood imported from abroad — a notion international scientists reject. WHO has said it is very unlikely that people can be infected with COVID-19 via packaged food, and that it is “highly speculative” to suggest COVID-19 did not start in China. Bi did not respond to requests for an interview, and China has not provided enough virus samples for a definitive analysis.

    We would be remiss if we didn't note that the now-destroyed Wet Market was located roughly 900 feet from a China CDC aboratory where they were experimenting on bat coronavirus.

    Read the rest of AP's report here.

    https://www.zerohedge.com/covid-19/chinas-clampdown-covid-19-origins-exposed-ap-journalists-tailed-samples-seized