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Wednesday, May 1, 2024

Daszak Testifies Days After Whistleblower Documents More Dangerous Wuhan Research

 British epidemiologist Peter Daszak, EcoHealth Alliance, is testifying today in front of Congress, where Congressional investigators will try and get to the bottom of multiple inconsistent statements he's made about gain-of-function research which took place at the Wuhan Institute of Virology.

Watch live here (due to start at 1000ET):

Hours before Daszak's testimony, the House Select Subcommittee on the Coronavirus Pandemic released a staff-level report recommending that Daszak be formally disbarred and criminally investigated as a result of his actions prior to and during the COVID-19 pandemic. Key findings include:

  • EcoHealth used U.S. taxpayer dollars to facilitate gain-of-function research on coronaviruses at the Wuhan Institute of Virology in China.

  • EcoHealth violated the terms and conditions of its NIH grant by failing to report a potentially dangerous gain-of-function experiment conducted at the WIV.

  • EcoHealth also violated NIH grant requirements when it failed to submit a required research update report until nearly TWO YEARS after the NIH deadline.

  • The Trump Administration identified serious concerns with EcoHealth Alliance’s funding of the WIV and instructed NIH to fix the problem. Then, NIH terminated EcoHealth’s grant.

  • NIH is currently violating the terms of the WIV’s formal debarment by funding EcoHealth’s research.

Meanwhile on Monday, journalist Paul Thacker revealed a new set of documents which raise further questions into the work done by Daszak, as well as statements made by the National Institutes of Health regarding papers showing they funded risky virus research at the Wuhan Institute of Virology to create dangerous chimeric viruses.

As Thacker writes at The Disinformation Chronicle (which you should really subscribe to if you haven't already), and reprinted with permission (emphasis ours),

*  *  *

EcoHealth Alliance president Peter Daszak notified NIH funders that EcoHealth Alliance planned to conduct risky virus research at the Wuhan Institute of Virology (WIV), in a June 2016 letter, many months before a pause on such research was lifted in 2017. When the NIH released some of this information in 2021, they assured Congress and the public that these chimeric virus studies could not have led to the COVID virus, but they did so in a public statement that cited research the NIH itself had funded at the WIV.

The documents also show that, after once making a pretense of overseeing EcoHealth Alliance’s grants, the NIH is now happy to coordinate messaging with Peter Daszak’s nonprofit. 

“Please pass this information on to the people at NIAID who need to coordinate communications,” Daszak wrote to NIH official Erik Stemmy, attaching a draft of a May 2023 press release. “And I'm available this evening, all day Friday and any time over the weekend to discuss.”

The 611 pages of new documents were provided to The DisInformation Chronicle by the whistleblower nonprofit Empower Oversight, which has sued the NIH to gain access to public records. Neither NIH spokeswoman Renate Myles nor EcoHealth Alliance’s Peter Daszak returned numerous requests for comment.

Controversy over EcoHealth Alliance’s risky research on MERS and SARS viruses first erupted in an October 2021 investigation by The Intercept, which reported that the WIV conducted dangerous virus experiments that the NIH was not fully aware of. The Intercept discovered these experiments in a missing 2019 report for an EcoHealth Alliance grant titled, “Understanding the Risk of Bat Coronavirus Emergence.”

The NIH first withheld the 2019 report from The Intercept, only to later provide it after they were sued. The Intercept also discovered that the 2019 report was inexplicably dated August 2021.

That summary of the group’s work includes a description of an experiment the EcoHealth Alliance conducted involving infectious clones of MERS-CoV, the virus that caused a deadly outbreak of Middle East respiratory syndrome in 2012. MERS has a case-fatality rate as high as 35 percent, much higher than Covid-19’s. The scientists swapped out the virus’s receptor-binding domain, or RBD, a part of the spike protein that enables it to enter a host’s cells, according to the report. “We constructed the full-length infectious clone of MERS-CoV, and replaced the RBD of MERS-CoV with the RBDs of various strains of HKU4-related coronaviruses previously identified in bats from different provinces in southern China,” the scientists wrote.

After reviewing the documents for The Intercept, Jack Nunberg, a virologist and director of the Montana Biotechnology Center at the University of Montana, told reporters, “Changing the receptor binding site on MERS is sort of crazy.” Nunberg added, “Although these new chimeric viruses may retain properties of the MERS-CoV genetic backbone, engineering of a known human pathogen raises new and unpredictable risks beyond those posed by their previously reported studies using a non-pathogenic bat virus backbone.”

However, new documents show that EcoHealth Alliance proposed these experiments to the NIH’s Erik Stemmy in a June 2016 letter—three years before Chinese researchers at the WIV purportedly conducted them in 2019. This is also five years before EcoHealth Alliance submitted their report of these experiments to the NIH, which is dated August of 2021.

The date when these chimeric virus experiments were conducted is crucial, as the White House allegedly stopped funding these type of studies in 2014. MERS is known to infect and spread in humans, and was specifically designated under the NIH’s pause on funding gain-of-function research of concern.

“Public involvement in this deliberative process is key, and the process is thus designed to be transparent, accessible, and open to input from all sources,” reads the governments statement on the funding pause, which ended sometime in 2017.

However, in a June 2016 letter, almost a year before the pause was lifted, Daszak described these same risky experiments with MERS and SARS viruses that the White House alleged were no longer being funded. “We have provided the details you requested, below, including alternative strategies if we remove work that could be deemed gain of function,” Daszak wrote to the NIH’s Erik Stemmy.

While The Intercept reported that the WIV allegedly conducted the risky research in year five of the grant, Daszak told the NIH in the 2016 letter that the virus research was proposed for year 3 of the grant. This date should have placed the experiments within the timeframe when the White House had ceased funding such research—a pause which was lifted in 2017.

When The Intercept reported in 2021 on these virus experiments—alleged to have taken place in 2019—the NIH sent Congress a letter to explain reported discrepancies in risky research that EcoHealth Alliance conducted at the WIV.

“NIH says ‘no NIAID funding was approved for Gain of Function research at the WIV.’” Republicans on the House Oversight Committee tweeted, attaching a copy of the NIH’s letter. “Obviously, they were lied to. NIH confirmed today EcoHealth and the WIV conducted GOF research on bat coronaviruses.”

The NIH also posted a statement at that time claiming the WIV research they had funded could not have created the SARS virus that caused the pandemic.

The chimeric viruses that were studied (i.e., the WIV-1 virus with the various spike proteins obtained from bat viruses found in nature) were so far distant from an evolutionary standpoint from SARS-CoV-2 (Figure 1) that they could not have possibly been the source of SARS-CoV-2 or the COVID-19 pandemic.

The NIH’s statement cited three peer reviewed studies as evidence that chimeric viruses created by EcoHealth Alliance at the WIV could not have led to the COVID-19 virus. Two of these studies were funded by the NIH and were published by EcoHealth Alliance’s Peter Daszak and Chinese researchers at the WIV. A third study the NIH cited was funded by the Chinese government and was published by Chinese researchers at the WIV.

The new documents also show that Congress and the media forced NIH officials to carefully script their responses about EcoHealth Alliance’s grants and research. The day before The Intercept’s story broke, NIH officials passed around flip cards for Anthony Fauci with a timeline of EcoHealth Alliance grants. NIH also included talking points Fauci could use regarding essays that had appeared in the Wall Street Journal and the Los Angeles Times.

The following day, The Intercept published their investigation, and the NIH’s Renate Myles passed around a reactive statement for the media and Congress as well as possible questions the NIH might receive along with approved answers.

“CLOSE HOLD: For Internal Use Only,” reads the October 21, 2021, NIH email subject line. “Final reactive statement and QA on the progress report are attached for use in responding to media and congressional inquiries,” Myles emailed.

An official in the NIH Director’s office emailed around news clippings the following day to keep everyone on message. “We anticipate more articles later today, and will update these clips with those articles once they pop. Let us know if you have questions.”

Emails show that The Intercept investigation also spurred multiple Hill briefings. “Last week NIH Deputy Director Larry Tabak briefed multiple Congressional committees on the Year 5 Progress Reports from the NIAID grant to EcoHealth Alliance,” reads a November email. “We received multiple follow-up questions (attached) that we would appreciate you taking a first pass at drafting responses.”

As has become NIH policy, much of the discussion in these emails is highly redacted, with entire pages sometimes blacked out.

To respond to an Inspector General audit of EcoHealth Alliance’s grants, NIH pulled in officials from all across the agency, including legislative affairs, the communications office, Anthony Fauci’s office, and the office of then-Director Francis Collins.

“Tracked changes show NIH OD edits to NIAID's most recent input as well as OCGR-Leg's recommended counter edits,” reads a November 2021 email.

By April of 2023, the NIH began coordinating directly with EcoHealth Alliance to prepare for renewal of the controversial grant that caused so many headaches. In an email to Peter Daszak, NIH’s Erik Stemmy advised him to update the grant’s language as reported in the NIH’s grants database to “reflect the revised work for that award.”

“No problem at all Erik,” Daszak responded. “Very happy to see that things will be moving forwards. We have a lot of work to do on the grants management extra oversight, but all that is fixable.”

Before submitting changes to the NIH database, Daszak ran the language past NIH’s Erik Stemmy on May 3. “Could you quickly read through and check - we can make further edits if you think there is anything here that could be worded better for the public understanding of our work, given that there will likely be interest in it.”

“Thanks for sharing the draft update, will get back to you ASAP!” Stemmy replied, later emailing Daszak, “Looks like it accurately reflects the renegotiation so please go ahead with the update.”

On May 4, 2023, Daszak forwarded Stemmy the draft of EcoHealth Alliance’s press statement announcing the grant renewal. “As per our Notice of Award requirements, and to make sure we can coordinate public discussion about the grant, I'm emailing to notify NIAID in advance that we're aiming to make a public statement.”

When EcoHealth Alliance published their announcement on May 8, 2023, the statement noted that they would not be conducting any gain-of-function virus experiments, the very research they had denied conducting in the past.

“It clarifies that the work does not involve recombinant virus technology, dual use research of concern, nor experiments intended to enhance the virulence or transmissibility of human pathogens (so-called ‘gain of function’ research).”

TIMELINE

JUNE 2016: Peter Daszak of EcoHealth Alliance notifies NIH that they plan to make chimeric MERS and SARS viruses in year 3 of a bat coronavirus grant.

2017: NIH lifts pause on research involving chimeric MERS and SARS viruses.

SEPTEMBER 2021: EcoHealth Alliance emails The Intercept that EcoHealth Alliance had not conducted MERS research. “The MERS work proposed in the grant is suggested as an alternative and was not undertaken.”

That same month, Peter Daszak emails several researchers and NIH officials that EcoHealth Alliance proposed the MERS research “and then pushed it to [year] 4. In the end we didn’t do this work.”

OCTOBER 20, 2021: To get out ahead of a coming investigation by The Intercept, NIH notifies Congress that EcoHealth Alliance performed risky research on chimeric MERS and SARS viruses “during the 2018-2019 grant period.”

OCTOBER 21, 2021: The Intercept reports that EcoHealth Alliance performed risky MERS studies in China, according to a year 5 grant report by EcoHealth Alliance.

That same day, the NIH alleges EcoHealth Alliance research conducted at the WIV could not have led to the pandemic, citing three peer reviewed studies the NIH and Chinese government had funded at the WIV.

MAY 2023: EcoHealth Alliance coordinates on public statements with NIH officials to announce the agency has renewed their grant, but the research will not involve risky research to make chimeric MERS and SARS viruses.

*  *  *

https://www.zerohedge.com/medical/watch-peter-daszak-testifies-days-after-whistleblower-documents-expose-more-about-dangerous

CVRx results, outlook miss

CVRx (NASDAQ:CVRX) stock is falling hard on Wednesday after posting results from its earnings report for the first quarter of 2024.

The bad news for investors in CVRX stock starts with its earnings per share of -$1.04. That’s much worse than the -54 cents per share Wall Street was expecting. It’s also wider than the -55 cents per share from the same period of the year prior.

Adding to this is CVRx’s revenue of $10.77 million. That’s another miss next to analysts’ estimate of $11.37 million for the quarter. However, it is up 35% year-over-year from $7.98 million.


CVRx’s guidance for the second quarter of 2024 has it expecting revenue to range from $11.3 million to $12.3 million. That would see it miss Wall Street’s Q2 revenue estimate of $13.12 million.

The company’s outlook for the full year of 2024 isn’t much better. It expects revenue for the year to come in between $50 million and $53 million. That would also fail to reach analysts’ estimate of $55.21 million for the year.


https://investorplace.com/2024/05/why-is-cvrx-cvrx-stock-down-32-today/

TransMedics revenue soars, guidance upped

  • Total Revenue: $96.9 million, a 133% increase year-over-year and 19% sequentially from Q4 2023.

  • TransMedics Transplant Logistics Service Revenue: $14.5 million, up 58% from $9.2 million in Q4 2023.

  • Gross Margin: 62%, increased from 59% last quarter.

  • GAAP Operating Profit: $12.4 million, representing 13% of total revenue.

  • Net Income: $12.2 million.

  • Annual Revenue Guidance: Updated to $390 million to $400 million, indicating 61% to 66% growth over full year 2023.

Surmodics Updates Fiscal Year 2024 Financial Guidance

 

Announces Commercial Launch of Two New Thrombectomy Devices for the Venous and Arterial Vasculatures: Pounce™ Venous and Pounce LP (Low Profile)

Surmodics, Inc. (Nasdaq: SRDX), a leading provider of medical device and in vitro diagnostic technologies to the healthcare industry, today reported financial results for its second quarter ended March 31, 2024, and updated financial guidance for its fiscal year ending September 30, 2024.

Second Quarter Fiscal 2024 Financial Summary

  • Total Revenue of $32.0 million, an increase of 18% year-over-year
  • Total Revenue excluding SurVeil™ drug-coated balloon (“DCB”) license fee revenue(1) of $30.9 million, an increase of 19% year-over-year
  • GAAP net income of $0.2 million, compared to a net loss of $(7.7) million in the prior-year period
  • Adjusted EBITDA(2) of $4.8 million, compared to $(1.5) million in the prior-year period

Second Quarter and Recent Business Highlights

  • On January 22, 2024, Surmodics announced the successful early clinical use and limited market evaluation (LME) of the Pounce LP (Low Profile) Thrombectomy System, which is designed for removal of acute-to-chronic thrombi and emboli in peripheral arteries ranging from 2 mm to 4 mm, such as those found below the knee.
  • Today, Surmodics is announcing the completion of LME and commercial launch of two new mechanical thrombectomy systems for the peripheral venous and arterial vasculatures, the Pounce Venous Thrombectomy System and the Pounce LP Thrombectomy System.
    • The Pounce Venous Thrombectomy System, which transitioned to commercial launch in March, is designed to remove mixed-morphology, wall-adherent peripheral venous clot in a single treatment session while minimizing the need for thrombolytics.
    • The Pounce LP Thrombectomy System, which transitioned to commercial launch in April, addresses an important unmet need for the prompt removal of acute-to-chronic thrombi or emboli in below-the-knee arteries 2 to 4 mm in diameter while minimizing the need for thrombolytics.

TG Therapeutics Inc (TGTX) Surpasses Revenue Estimates in Q1 2024, Despite Widening Net Loss

 

  • Total Revenue: Reported $63.5 million in Q1 2024, surpassing estimates of $54.58 million.

  • Net Loss: Recorded at $10.7 million for Q1 2024, significantly below the estimated net loss of $4.13 million.

  • Earnings Per Share: Actual EPS of -$0.07, fell short of the estimated -$0.04.

  • Product Revenue Growth: BRIUMVI U.S. net product revenue reached $50.5 million, indicating over 25% growth quarter over quarter.

  • R&D Expenses: Increased to $32.7 million in Q1 2024 from $15.9 million in the same period last year, driven by development costs and licensing expenses.

  • SG&A Expenses: Rose to $34.6 million due to scale-up activities for BRIUMVI's commercial launch.

  • Cash Position: Ended the quarter with $209.8 million in cash, cash equivalents, and investment securities.

The first quarter of 2024 saw TG Therapeutics achieve a total revenue of $63.5 million, significantly higher than the analyst estimate of $54.58 million. This includes $50.5 million from BRIUMVI U.S. net product sales, marking over 25% growth quarter over quarter, and a $12.5 million milestone payment related to BRIUMVI's launch in the first EU country. Despite these gains, the company recorded a net loss of $10.7 million for the quarter, a notable improvement from the $39.2 million loss in Q1 2023 but still higher than the estimated net loss of $4.13 million.

Operational and Development Milestones

During Q1 2024, TG Therapeutics continued to expand its commercial and clinical footprint. The company secured a national contract with the Department of Veterans Affairs, making BRIUMVI the preferred anti-CD20 antibody for RMS. On the development front, efforts are underway to enhance BRIUMVI's dosing convenience and to expand its indications beyond MS.

Financial Health and Future Outlook

As of March 31, 2024, TG Therapeutics reported having $209.8 million in cash, cash equivalents, and investment securities. This robust financial position is expected to support ongoing operations and fund further development activities. The company has updated its 2024 revenue guidance for BRIUMVI in the U.S. to range between $270 million and $290 million.

https://finance.yahoo.com/news/tg-therapeutics-inc-tgtx-surpasses-123417768.html

CytomX Initial CX-904 Phase 1a Clinical Data Update on May 8

- CX-904 (masked EGFRxCD3 Probody® T-cell engager) preliminary Phase 1a results to be presented from ongoing dose escalation study -

- Management to hold conference call at 5 p.m. EDT / 2 p.m. PDT on May 8th-

Participants may access the live webcast of the conference call from the Events and Presentations page of CytomX’s website at https://ir.cytomx.com/events-and-presentations. Participants may register for the conference call here and are advised to do so at least 10 minutes prior to joining the call. An archived replay of the webcast will be available on the Company’s website.

https://www.globenewswire.com/news-release/2024/05/01/2873162/37704/en/CytomX-Therapeutics-to-Report-First-Quarter-2024-Results-and-Provide-an-Initial-CX-904-Phase-1a-Clinical-Data-Update-on-May-8-2024.html

Drug Companies, VCs Rethink R&D Strategies as IRA Stands Strong in Court

 Big Pharma took another hit in court Monday as a federal judge in New Jersey threw out challenges by Johnson & Johnson and Bristol Myers Squibb to the drug price negotiations outlined in the Inflation Reduction Act. AstraZeneca and trade group Pharmaceutical Research and Manufacturers of America (PhRMA), along with several provider-side allies, have already lost their legal challenges to the 2022 law, and the Centers for Medicare and Medicaid Services is pushing ahead with negotiations over the first 10 drugs in the program.

Those negotiated rates will take effect in 2026, and pharma companies are now reconsidering their R&D strategies as the venture capital community ponders where to focus its investments. One big consideration is the IRA’s so-called “pill penalty,” which caps patent protection at 9 years for small molecules, compared with 13 years for biologics.

Drug development had already been trending toward biologics. This drug class received 30% more VC funding in 2022 than small molecule candidates, noted John Stanford, executive director of life sciences venture capital coalition Incubate—but the gap jumped to 50% in 2023, and Stanford contends that the IRA is driving much of that shift.

“If your promising product is a small molecule, the VC community is far less interested than we were before the IRA,” Stanford told BioSpace. “It makes no sense for people to invest when you can get 9 years’ return, just from the economic standpoint.”

Pfizer was the first Big Pharma firm to cite the IRA when it decided to shift its oncology R&D strategy to focus more on antibody-drug conjugates and bispecific antibodies and less on small molecules. Stanford also noted that Vir Biotechnology discontinued its innate immunity small molecule pipeline and that Protagonist Therapeutics has announced plans to discard a small molecule treatment for ulcerative colitis.

Not everyone has pivoted just yet, though. Eli Lilly has said the company is not terribly concerned about potential price negotiations for hot-selling GLP-1 drugs, and Mark Rutstein, senior vice president and head of global oncology clinical development at Daiichi Sankyo, said his company is watching the Medicare negotiations play out but not immediately changing its strategy.

There will be other IRA considerations besides the pill penalty, said Christiana Bardon, co-managing partner of biotech investment firm MPM BioImpact. Because the patent protection clock starts at the first approval, “biotech and pharma companies . . . won’t launch small indications first,” she told BioSpace.

The legal battle is far from over. BMS and AstraZeneca have appealed the judgments against them, and PhRMA said this week that it would soon do the same. With these appeals and several other IRA challenges still pending, it remains to be seen how Medicare drug price negotiations will play out, and even more uncertain are the details of shifting biopharma strategies. But what is clear is that it’s complicated.

“R&D is going to be tied to not just good science, but the commercial realities associated with a product,” Stanford said.

Wide-Ranging Investment Considerations of the IRA

Although small molecules have a shorter period of protection, all new drugs could potentially be up for price negotiations before than would likely be losing patent-protected exclusivity. Prior to the 2022 law, the average time for patent protection was 14.4 years across the board, according to Bardon, and Medicare had no power to negotiate prices.

Bardon said that the IRA will ultimately affect the net present value of drugs, or the total amount of money that products could make over their lifespans, and it will cause shifts in strategy to buffer against losses.

For example, drugmakers will be looking for common indications with large potential markets to recoup as much of their investment as possible in a shorter timeframe, she said. In the past, biopharma firms would launch new drugs in smaller patient populations where the data might be stronger while also running trials in populations with greater market opportunity.

“Nowadays, I think that won’t happen anymore,” Bardon said. “We have to launch right away with the bigger indications,” likely hindering development of therapeutics for rarer diseases.

“Instead of having one drug that treats disease A, B and C, I'll have drug one treat disease A, then I’ll have a follow-on drug two which treats disease B, and then I’ll have a follow-on drug three which treats disease C,” she continued. “Incrementally, that would protect our revenue, but it does create additional R&D overhead,” making the system less efficient and forcing patients with rarer conditions to wait longer for new medications. Indeed, a study published in February suggested that the IRA could discourage companies from seeking approvals for secondary indications. 

Another consequence of the IRA comes from the modifications it brings to the Medicare Part D program—specifically, the capping of individual out-of-pocket drug spending, which the Congressional Budget Office has estimated to reduce drug spending by $100 billion over the next 10 years. “It’s a huge slice out of an industry over the next 10 years, which is already causing R&D budgets to contract,” Stanford said.

The consequence, he said, is that biopharma investments will focus on “the safest science.” This includes “me-too” drugs that are similar to previously approved products and thus are lower-risk. One of the ironies of the IRA, then, according to Stanford, is that the law has incentivized making the exact type of drugs that lawmakers have previously criticized because they do not always advance the quality of healthcare.  

As for the pill penalty, Stanford said that drugs make about half of their revenues in years 10–13 following approval. So, for small molecules to be potentially subject to price negotiations at 9 years would cut out a ton of profit for the companies. That means that startups or early-stage firms seeking private investment simply should not try to pitch small molecules, Stanford said. “Just simply don’t. Reformulate as a biologic because that is what Congress is telling us to do.”

Bipartisan legislation introduced this year would remove the discrepancy between small molecules and biologics by setting the grace period for all drugs at 13 years, but Stanford said he is skeptical that it could pass before the presidential election in November. “We’re hoping that after the election, common sense might prevail during the lame-duck session.”

In its current form, however, the IRA is stunting drug development, said Stanford, who used a baseball analogy to hammer home his point. “You’ve made it so the industry should hit singles and doubles, and you’ve made it almost impossible to take the risk of hitting a home run.”

https://www.biospace.com/article/drug-companies-vcs-rethink-r-and-d-strategies-as-ira-stands-strong-in-court/