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Tuesday, September 14, 2021

Bill Gates on how public health has fared amid pandemic

 The Covid-19 pandemic has, of course, been devastating over the past year. But by other measures of public health, the year wasn’t quite as calamitous as Bill Gates and Melinda French Gates feared when they wrote their annual report in 2020.

That doesn’t mean the first year of the Covid pandemic hasn’t been hard.

The foundation’s 2021 Goalkeepers report, published late Monday, shows an additional 10 million children around the globe didn’t get key childhood vaccines this past year, because of public health service disruptions. Another 31 million people were pushed into extreme poverty by the pandemic. And employment among women is expected to remain 13 million jobs lower around the world this year than it was in 2019.

Covid-19 has deepened what was already a profound chasm between the rich and the poor, Bill Gates told STAT.

“Every dimension of inequity — rich versus poor in the U.S., inner city schools versus suburban schools, Blacks versus Caucasians, rich countries versus middle-income versus low-income [countries] — this has exacerbated every dimension of inequity that I can think of,” Gates said.

Gates spoke to STAT as part of a wide-ranging interview timed to the release of the Goalkeepers report. Excerpts from the interview have been lightly edited for clarity and length.

What are the things that you found most concerning in the Goalkeepers Report this year?

The most concerning thing is the economic situation in low-income countries. Their economic losses are very high and they’re not able to stimulate their economies in the same way that most of the rich countries and some of the middle-income countries have done. And the indebtedness levels are building up. So the borrowing is going to be restricted. That was true even before the pandemic, but it’s gotten worse now.

And so the extreme poverty number in some ways is the most depressing number. And global trade, tourism into the low-income countries — all of those things, there’ll still be some lower level of activity for several years to come. Particularly if you end up with a situation where Covid is still circulating in these low-income countries and so people are making it hard to travel in or travel out, just to restrict the spread of the disease.

Up until the Delta variant came along, the low-income countries … were not having nearly as bad an epidemic as almost all the middle-income and rich countries, for a variety of reasons. Young age, outdoor work and … a lot of the populations are out there in the rural areas. Now, although it’s still not dire in most African locations, if you look at the Institute for Health Metrics and Evaluation figures, they are forecast to have a fair number of deaths. So they’re going to get hit hardest at the tail.

Some of the things did not go exactly as we expected. The [non-Covid] vaccination rates so far only dropped by 7%, and we had predicted that that might go down by 14%. Malaria deaths, which we predicted might go up quite a bit, have actually stayed flat, partly because we have been able to get the [treated] bed nets out. The Global Fund [to Fight AIDS, Tuberculosis and Malaria] has done a very good job on that. But the economic numbers are sort of the ultimate measure that poor countries have had a very bad epidemic just because of the economic factors.

Your foundation likes to focus on the positive, trying to encourage people to effect change by highlighting the positive as opposed to always the negative. But just last week the annual report of the Global Fund came out and it had a much more dire take on some of the metrics in your report. Do you ever wonder whether focusing on the positive downplays the urgency of the situation?

There’s a tradeoff. If you don’t explain the progress the world has made in reducing poverty and reducing childhood deaths, then you’re really not creating an accurate picture.

There really is good news there. And I think if you only give the bad news — which both on health stuff and climate, sometimes that’s how messages are delivered — people might think, well, it’s hopeless, I should just go ignore all this stuff.

So I think we struck a pretty good balance. But now with the Delta wave, we have to acknowledge that we’re not at the end yet. And we fell short on getting vaccines out everywhere that we should have.

Did you expect we’d be closer to the end of the acute phase of the pandemic than we are at this point?

There’s two big things that have made things less far along in getting to the end than I expected. One is that a number of the vaccines have just taken longer to ramp up big manufacturing — and that includes Novavax and Johnson & Johnson. I’m in no way impugning those companies. This is hard stuff, new stuff. So it’s very complicated. I was, in retrospect, over-optimistic about ramping up the volume of those vaccines.

And the second thing is the Delta variant. Its transmissiveness, because of how well it replicates in the respiratory tract, is worse than I expected. And so those are two big things that have delayed having the supply side of vaccines fixed. But even once we get that solved, which we will in the next six months, we’ll still have the logistics of delivery, which are very tough in low-income countries.

The report calls the inequity in vaccine distribution between upper-income countries and low- and middle- income countries “a profound moral outrage.” It also talks about the need to build up production capacity in different parts of the world. But that’s a solution for the next pandemic. How does the problem get solved now?

As we get the supplies fixed over the next six months, the volumes of all vaccines will go up. [But] some people are getting picky now and, we’ll see who’s willing to take AstraZeneca, who’s willing to take the Chinese vaccines. If everybody wants to wait just for the mRNA, then that pushes the supply challenges out even further into the future.

But we are going to hit very quickly the logistical and demand limitations. And so that’s why the foundation, looking at where we have low routine immunization coverage — as places like Nigeria, Democratic Republic of Congo — we really need to get in and build now, take some of the tactics we used in polio and use those to build up capacity. But the demand, you know, is not that great, partly because the epidemic hasn’t been that bad. That’s a paradox: The better you do, the less demand you have.

You mentioned polio and I’m wondering: Are you concerned about what’s happening in Afghanistan and the prospects that might have for finally snuffing out wild polio?

Wild polio is only in Pakistan and Afghanistan. And actually, the number of cases in both countries is fairly low right now, partly because the coronavirus restrictions also reduced the transmission of polio. And so even though we don’t know how people will be able to do vaccinations in Afghanistan — that’s a very uncertain situation, it could be a huge problem or it could be OK — Pakistan has always been where most of the cases are.

And there we do have a good relationship with the government and they can see that the cases are very low and they’re very appreciative that the polio [campaign] infrastructure came along to help out with the Covid pandemic. And so, in some ways, they really want to finally get rid of that sort of stain on Pakistan, that they’re one of the last two countries. So, I can’t give you much visibility about Afghanistan, but I know the Pakistan situation is pretty hopeful.

And we are talking to the U.S. government about increasing the amount, actually doubling the amount they put into this, to get up to the same level as the foundation does, which is over $400 million a year. The U.S. up to now put in about $200 million a year.

We do think we can succeed in the next three years. But the pandemic was a huge setback.

Last year when we spoke about the Goalkeepers Report, I asked you about your thoughts about the U.S. response to the pandemic. You describe it as shocking. How do you feel about the state of the U.S. response now?

It’s still embarrassing that even though we were at the front of the line for all the vaccines, yet because of demand issues, the U.S. is well behind most of the Western European countries at this point.

You mean because of vaccine hesitancy?

Yeah — which I call demand.

Now that Delta’s here, it means there’s a lot of elderly people, some of them with weak immune systems or some who just chose not to get vaccinated, that are at risk. And it’s too bad. When we show that death number we should show, every day, that it’s the unvaccinated, overwhelmingly who are dying.

So the U.S. situation, there’s nothing that is as good as we’d like. And of course, people are tired of some things that are really bad, like not having school in. So we’re going to have school in, which I happen to agree with.

But they’re also tired of mask compliance. And that’s unfortunate because the mask inconvenience isn’t great, but it’s kind of a magical tool. We’ve been talking with a lot of pharmaceutical companies about inhaled blockers that would be a sort of new class of thing that would reduce your infection, but also prevent you from transmitting or getting sick. In fact, even the very best inhaled blocker would only match what a mask can do. Now, it might be more acceptable, but masks are hugely effective intervention. But, you know, people’s tiredness and the lack of clear message about those mean that this fall’s going to be tougher than it should be.

Last question: Did the U.S. ever get testing right?

We never got testing right. We’ve got in our innovation tool box solutions for diagnostics. And I’m a little surprised the U.S. hasn’t been more aggressive on those things.

Same with therapeutics. The ability to prove that things don’t work and prove things work continues to be not very well-coordinated. And the idea of how do you align these trials and get that stuff happening quickly, there’s still some outstanding thinking that we’ll need both for this pandemic and the next pandemic.

https://www.statnews.com/2021/09/13/gates-goalkeepers/

AI drug hunter Exscientia plans to go public with Nasdaq IPO

 After penning a major funding round earlier this year, the artificial intelligence-powered drug designer Exscientia is showing no signs of slowing down, with the announcement of plans to go public. 

The Oxford, U.K.-based developer confidentially filed for a $100 million Nasdaq IPO in late June, shortly after posting a $225 million series D that could include an additional $300 million in equity. The offering's exact pricing terms have not yet been disclosed, according to Renaissance Capital, and could climb higher.

Those proceeds will come alongside a recent $35 million equity investment from the Bill & Melinda Gates Foundation, which will support at least five small molecules aimed at COVID-19, influenza and other viruses that may spur the next global pandemic. Exscientia is set to provide matching funds for the effort.

The company’s pipeline is spearheaded by three AI-designed drug candidates that have begun phase 1 clinical trials, including one immuno-oncology agent for solid tumors in partnership with Evotec and two psychiatry-focused assets being co-developed with Sumitomo Dainippon.

Behind them are more than 25 active projects in cancer, inflammation and rare diseases, Exscientia said in its prospectus, including four potential drugs lined up for IND submissions with biopharma partners such as Bristol Myers Squibb and GT Aperion Therapeutics.

Using its AI programs to speed up design and discovery work, Exscientia claims it can cut the total amount of time needed by 70%—its most advanced programs have reportedly gone from target identification to candidate selection in less than 18 months, down from the industry average of four-and-a-half years.

That pitch attracted the attention of SoftBank this past April, with its Vision Fund 2 leading the company’s $225 million series D round. That fundraising also included the international conglomerate's commitment to an additional $300 million in equity funding, available for Exscientia to tap at its discretion.

Since then, Exscientia collected a $20 million payout in its $1.2 billion drug design partnership with BMS after landing on an immune-system modulating candidate while chasing a previously hard-to-hit target. BMS has in-licensed the drug and is set to take command of its clinical and commercial development.

This past summer also saw Exscientia spend some of its haul on the $60 million acquisition of Allcyte, an Austrian AI developer looking to predict how well cancer therapies perform in individual patients. Exscientia also inked a collaboration with EQRx to find low-cost options for cancer treatments.

Meanwhile, Exscientia’s contemporaries in AI-powered drug discovery have also seen their wallets swell: Recursion posted a $436 million IPO on the heels of a $239 million series D, while insitro and Insilico Medicine have collected $400 million and $255 million rounds, respectively.

https://www.fiercebiotech.com/medtech/ai-drug-hunter-exscientia-plans-to-go-public-nasdaq-ipo

Emergent to make Providence Therapeutics potential COVID-19 vaccine

 Emergent BioSolutions Inc signed a five-year agreement with Canadian biotechnology company Providence Therapeutics to develop and manufacture its COVID-19 vaccine candidate for about $90 million.

Emergent will produce drug substances for Providence's vaccine candidate, PTX-COVID19-B, as well as provide services for finished products such as filling the vaccine in vials at its Winnipeg facility in Canada.

The vaccine uses the messenger RNA (mRNA) technology, also used in COVID-19 shots developed by Moderna Inc and Pfizer Inc. Providence's vaccine is currently being tested in a mid-stage trial in Canada.

Emergent expects to manufacture tens of millions of doses of Providence's shot in 2022, as well as batches of formulated bulk drug substance for the vaccine with the potential to yield hundreds of millions more doses.

The agreement covers cost for manufacturing services, studies to support global supply chain activities, as well as facility and equipment investments, the companies said on Tuesday.

https://finance.yahoo.com/news/1-emergent-providence-therapeutics-potential-123233208.html

Axsome: FDA accepts application for acute migraine treatment

 Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing novel therapies for the management of central nervous system (CNS) disorders, today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company’s New Drug Application (NDA) for AXS-07 for the acute treatment of migraine, and has set a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2022 for the NDA. AXS-07 (MoSEIC™ meloxicam-rizatriptan) is a novel, oral, rapidly absorbed, multi-mechanistic, investigational medicine for migraine.

“The FDA’s acceptance of the NDA for AXS-07 is an important milestone for Axsome as it brings us closer to potentially making this multi-mechanistic treatment available to migraine patients in need,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “We look forward to continued interactions with the FDA during the review process.”

The NDA is supported by results from two Phase 3 randomized, double-blind, controlled trials of AXS-07 in the acute treatment of migraine, the MOMENTUM and INTERCEPT trials, which demonstrated statistically significant elimination of migraine pain with AXS-07 compared to placebo and active controls.

https://finance.yahoo.com/news/axsome-therapeutics-announces-fda-acceptance-110000051.html

Novocure To Test Tumor Treating Fields With Roche Tecentriq In Pancreatic Cancer

 

  • Novocure Ltd  (Get Free Alerts for NVCR) has entered into a clinical trial collaboration agreement with Roche Holdings AG  (Get Free Alerts for RHHBY) to develop Tumor Treating Fields (TTFields) together with Roche's atezolizumab in metastatic pancreatic ductal adenocarcinoma (mPDAC).
  • The phase 2 study was designed to test the safety and efficacy of TTFields together with atezolizumab, gemcitabine, and nab-paclitaxel as a first-line treatment for mPDAC. 
  • The study will enroll approximately 75 patients with a primary endpoint of disease control rate.
  •  The secondary endpoints include overall survival, progression-free survival (PFS), one-year survival, objective response rate, PFS at six months, duration of response, and toxicity profile. 
  • Novocure is the study sponsor, and Roche is providing atezolizumab for the trial.
  • Tumor Treating Fields are electric fields that disrupt cancer cell division.
  • Last week, the FDA granted breakthrough designation to the NovoTTF-200T System, TTFields, to be delivered together with atezolizumab and bevacizumab for the first-line treatment of patients with unresectable or metastatic liver cancer.

RedHill: Top-Line Data from Opaganib Phase 2/3 Study in Severe COVID-19 Missed Endpoint

  RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, today announced preliminary top-line data from the 475-patient global Phase 2/3 study with opaganib (ABC294640)[1] in hospitalized patients with severe COVID-19 pneumonia.

Preliminary top-line data showed that the study did not meet its primary endpoint. Analysis of the study efficacy endpoints did show trends in favor of the opaganib arm vs. placebo across multiple endpoints, including the primary endpoint, despite not achieving statistical significance.

https://finance.yahoo.com/news/redhill-biopharma-reports-top-line-121500779.html


NanoViricides Completes Licensing for Coronavirus Field Including Current COVID Drug Development

 NanoViricides, Inc. (NYSE Amer.: NNVC) (the "Company"), a global leader in nanomedicines against viruses, announced today that it has completed the process of licensing the human Coronavirus field for drug development and commercialization from TheraCour Pharma, Inc. ("TheraCour"). The Company executed a license agreement for the field comprising anti-viral treatments for coronavirus derived human infections with TheraCour Pharma, Inc. on September 8, 2021 (the "Agreement").

NanoViricides is developing oral and pediatric drugs to fight COVID-19 designed to be effective against most variants.

The licensed field includes antiviral drugs to treat SARS-CoV-2 and its variants that cause the COVID-19 disease resulting in a global pandemic that continues to rage through the world, wave after wave, as new variants develop and take hold. There was no upfront cash payment for the license and the compensation terms were generally consistent with prior licenses, and are summarized further below.

NanoViricides is currently working on taking its two COVID-19 lead drug candidates, namely, NV-CoV-2- and NV-CoV-2-R, into human clinical trials. The Company believes that the essential preclinical work is substantially complete for taking these drugs into human evaluation.

The Company believes that these broad-spectrum anti-coronavirus drugs will continue to be effective even as the virus continues to mutate developing into a number of variants of concern. Antibody protection afforded by vaccines and the effectiveness of antibody drugs have continued to decline progressively as new SRAS-CoV-2 variants have emerged. The Company believes that its unique anti-viral nanomachine technology overcomes these issues.

The Company believes it is well poised to deliver an out-patient oral medicine to treat COVID-19 infections. The Company has found that its anti-COVID-19 drugs exhibited strong antiviral effectiveness when given orally in animal studies.

The Company also believes that its COVID-19 drugs will be suitable for use in pediatric patients, and we plan to include pediatric cohorts into clinical trials at the appropriate stages. We believe that pediatric use of these drugs is feasible based on the excellent safety profile we have observed in animal studies. As the variants evolve, pediatric infections and their severity have begun to rise, causing major worldwide concerns even as the world is trying to move towards normalcy in education and child social interactions.

The Company's anti-COVID drugs are based on polymeric micelle nanomedicine technologies developed by TheraCour Pharma, Inc. and its affiliate, AllExcel, Inc. The inventors have filed a PCT patent application that forms the basis of the Company's two lead drug candidates, namely, NV-CoV-2 and NV-CoV-2-R. The new patent application covers the new technologies, compositions, formulations, processes, manufactured products, and methods of use, among other specifics. This patent application was filed on June 25, 2021, application number PCT/US2007/001607, entitled "Self-Assembling Amphiphilic Polymers As Anti-Covid-19 Agents". Its nominal expiry date would be 20 years, after filing and if issued, i.e. June 24, 2041, and could be extended in certain countries under regulatory extensions to as late as into the year 2043, providing a significant commercial runway.

Under the Agreement, NanoViricides has obtained a world-wide, exclusive, sub-licensable, license to use, promote, offer for sale, import, export, sell and distribute antiviral drugs that treat human Coronavirus infections using TheraCour's proprietary as well as patented technology and intellectual property, including the new patent application cited above. The discovery of ligands and polymer materials as well as formulations, the chemistry and chemical characterization, as well as process development and related work will be performed by TheraCour under the same compensation terms as prior agreements between the parties, with no duplication of costs allowed.

NanoViricides will not make any upfront cash payments to TheraCour and has agreed to the following milestone payments to TheraCour: 100,000 shares of the Company's Series A Convertible Preferred Stock, par value $0.001 per share (the "Series A Preferred Stock") upon the execution of the Agreement; 50,000 shares of Series A Preferred Stock after the grant of the approval of Licensee's Investigational New Drug (IND) Application, or its equivalent; cash payments of $1,500,000 after the initiation of Phase I clinical trials or its equivalent; $2,000,000 after the completion of Phase 1 Clinical Trials or its equivalent for at least one product within twelve (12) months from the date of the acceptance of the IND; $2,500,000 no later than six (6) months after the completion of Phase 2A Clinical Trials or its equivalent for at least one product within twenty (24) months from the date of the completion of Phase 1 or its equivalent; 100,000 shares of Series A Preferred Stock after the initiation of Phase 3 clinical trials or its equivalent; and, at TheraCour's option, $5,000,000 in cash or 500,000 shares of Series A Preferred Stock, no later than six (6) months after the completion of Phase 3 Clinical Trials or its equivalent for at least one product within thirty-six (36) months from the completion of Phase 2 Clinical Trials or its equivalent. In addition, the Company agreed to pay to TheraCour fifteen percent (15%) of net sales of licensed products and any income from sublicensed products, consistent with previous agreements. Under the Agreement, TheraCour retains the exclusive right to develop and manufacture the Licensed Products. The Agreement contemplates that the parties will enter into a separate Manufacturing and Supply Agreement for the commercial manufacture and supply of the drug products if and when NanoViricides intends to engage into commercialization of the drugs. The Agreement provides that the Manufacturing and Supply agreement would be on customary and reasonable terms, on a cost-plus basis, using a market rate based on then-current industry standards, and include customary backup manufacturing rights, as with prior agreements.

https://finance.yahoo.com/news/nanoviricides-completes-licensing-coronavirus-field-104500583.html