Germany stakes its claim over Curevac

The German government will not get exclusive access to Curevac’s Covid-19 vaccine as part of its 23% stake purchase, the company insists.

Perhaps there was some truth behind reports of a strategic Covid-19 vaccine deal between the Trump administration and the German biotech company Curevac, resoundingly denied three months ago. The German government has bought a 23% stake in the mRNA researcher for €300m ($338m), it was revealed today.
The investment is not tied to any sort of exclusive access or supply arrangement over Curevac’s Covid-19 vaccine candidate, the company’s finance director, Pierre Kemula, told Evaluate Vantage. However it seems likely that alarm at the highest levels at the implications of such an arrangement – real or otherwise – had helped persuade the German government into this move.
“When Covid-19 appeared we had meetings with the government and said we could do with some support,” Mr Kemula said. The investment was “triggered by Covid, but it is not related to Covid directly”.
He did not rule out deals that might involve access in the future – for example when it comes to figuring out how to fund the large and expensive trials that will be required to test the company’s vaccine candidate thoroughly. For now, however, the government will remain a large shareholder, but with not have a board seat or a say over the company’s strategic direction.
Curevac’s mRNA-based vaccine candidate is poised to start trials in healthy volunteers. Speculation that the company’s former chief executive had talked about an exclusive supply agreement with the US sparked uproar in Germany back in March, and upheaval at the company (Crisis, what crisis? Curevac denies everything, March 17, 2020)
Long-term thinking
The €300m investment, which will be made via the country’s state-owned development bank, Kreditanstalt für Wiederaufbau, is a first for Germany. Partly it has been driven by a realisation that the country’s healthcare sector needs supporting; this has not “shined as brightly” as other parts of the economy, Mr Kemula said.
The money will be used to support Curevac’s research into various disease areas, but it seems clear that the German government is thinking both long and short term here. In a press release on the deal a German minister acknowledges that the Covid-19 pandemic has made securing medical supply chains a national security issue.
What the deal says about Curevac’s valuation is another question. The terms put the company’s worth at €1.3bn. This sounds low: an earlier financing was said to have been done at a $1.7bn valuation, and the market caps of mRNA peers Moderna and Biontech are substantially higher.
Mr Kemula declined to discuss what the company might be worth, but pointed out that its lead project, a prostate cancer vaccine, failed in early 2017. Such an event would certainly knock a valuation, although the subsequent revival in interest in mRNA would surely have helped Curevac to recover since then.
Either way, the company’s majority shareholder, the serial German biotech investor Dietmar Hopp, apparently supports the new financing. His 80% stake will be diluted accordingly.
As a decades-long and very generous backer of the country’s biotech scene Mr Hopp has always exhibited an ability to look long term. And, from his point of view, welcoming a deep-pocketed new partner to the party on generous terms could pay dividends in the future.
https://www.evaluate.com/vantage/articles/news/deals/germany-stakes-its-claim-over-curevac

ADA 2020 – Medtronic leads Insulet, but things could change

Medtronic’s newest closed-loop system posts decent pivotal data, but Insulet and Abbott are waiting in the wings.

This weekend’s data on the latest iteration of Medtronic’s artificial pancreas look good enough to secure US approval. The question is whether the MiniMed 780G controls patients’ blood sugar as well as rival technologies, and could thus allow Medtronic to slow the decline of its market share.
And today’s US market clearance of the long-awaited next generation of Abbott’s continuous glucose monitor ups the ante. The FreeStyle Libre 2 is one of the most effective blood sugar sensors available and also one of the cheapest, and could soon be available as part of a closed-loop system with Insulet’s Omnipod 5 insulin pump, impressive data on which also emerged on Friday.
Medtronic’s 780G was CE marked last week, but must still prove its worth to the US regulator. In the pivotal trial, data from which were presented at the virtual annual meeting of the American Diabetes Association on Friday, the device allowed type 1 diabetes patients’ blood sugar levels to remain in the safe range of 70-180mg/dl 75% of the time.
The trial had no control group, but all study subjects had previously been using either Medtronic’s earlier version of the system, the MiniMed 670G, or a different sensor-augmented pump. Comparing patient’s achievements at the end of the study with their baseline stats gives an indication of sorts of the 780G’s performance.
The patients did improve; unfortunately many of the improvements were marginal. Perhaps the most positive finding was that the amount of time the participants were happy to leave their device in auto mode jumped from 33% to 95%. In the pivotal trial of the 670G this was 87%, though likely lower in real life. Stifel analysts say this is a critical improvement over the 670G.

Minimed 780G pivotal data
	Baseline	Trial results
Time in range	68.8%	74.5%
Time in auto mode	33.4%	94.8%
Time in hypoglycaemia	4.1%	2.8%
Time in hyperglycaemia	34.1%	27.7%
Average A1C	7.5%	7.0%
Source: ADA 2020 Presentation.

The time in range is better than seen with some other artificial pancreas technologies, but not by much. The combination of Tandem Diabetes Care’s t:slim X2 insulin pump with Dexcom’s G6 continuous glucose monitor kept patients in range 71% of the time. And this system does not require patients to test their blood sugar with daily fingersticks for calibration, whereas Medtronic’s system requires maybe four or five of these each day.
Another rival technology whose performance must be considered is Insulet’s Omnipod 5. Formerly called the Omnipod Horizon, this insulin pump is intended to work with glucose sensors from Abbott and Dexcom – including the former’s newly available Freestyle Libre 2 (Collaborative diabetes tech on the Horizon, February 20, 2020).
The pivotal trial of the Omnipod 5 was halted in March to allow Insulet to correct a flaw in the software that could have caused the system to deliver the wrong quantity of insulin, though at the time no adverse events had been reported due to this issue. The trial resumed just over a week ago and ought to report towards the end of this year.
The ADA data come from a small, single-arm study. In 18 adults, time in range improved from 66% at baseline to 73%; in the 18 children in the trial this jumped from 51% at baseline to 65%. Patients had the device in auto mode 97% of the time, which Stifel analysts called “very impressive”.
Better and cheaper
If Insulet’s system can repeat this kind of performance in its pivotal trial approval, a planned launch in the first half of next year, is all but assured. Following that, a combination closed-loop system incorporating Abbott’s CGM is intended to follow.
The first version of the Freestyle Libre is the bestselling CGM in the US thanks in large part to its relative cheapness. Abbott said today that the Libre 2 will be sold at the same price as its forerunner, preserving this advantage, but it also has potentially best-in-class accuracy, and a paediatric indication. This label could meaningfully expand Abbott’s market in the US when the device is launched in late summer.
By the time any an artificial pancreas incorporating Omnipod 5 and Libre 2 reaches market, the 780G will likely have already been on sale for a year or more. Medtronic must make the most of this, because on current showing it does not have the technological edge.
https://www.evaluate.com/vantage/articles/news/trial-results/ada-2020-medtronic-leads-insulet-things-could-change

Provention Bio up 11% on positive teplizumab data

Provention Bio (PRVB +10.6%) is up on a 4x surge in volume in reaction to follow-up data from a Phase 2 study, “At Risk” TN-10, evaluating teplizumab for preventing/delaying the onset of type 1 diabetes (T1D) in relatives of type 1 diabetics deemed “at very high risk” of developing the condition.

Results showed that a single 14-day course of teplizumab significantly delayed the onset of T1D in presymptomatic patients by a median of three years compared to placebo.

In addition, declines in C-peptide levels (reductions indicate destruction of insulin-producing beta cells in the pancreas) in treated patients stabilized than reversed, suggesting possible restoration of insulin production by these cells.

Treatment with teplizumab resulted in 54% less risk of progressing to insulin-dependent T1D compared to placebo.

No new safety signals were observed.

The company expects to complete its U.S. marketing application in Q4.

Teplizumab is a CD3-targeted monoclonal antibody designed to slow the loss of insulin-producing beta cells in the pancreas while preserving beta cell function as measured by C-peptide.

https://seekingalpha.com/news/3583109-provention-bio-up-11-on-positive-teplizumab-data

COVID-19 cuts at least 10 states’ tax revenue by 30%

At least 10 U.S. states will see their tax collections shrink by more than 30% due to the COVID-19 pandemic, say researchers at Arizona State and Old Dominion universities.

On average, states’ tax revenue will fall ~20%, economists say.

New York’s tax collections are projected to fall 40% and Maine’s is expected to decline 39.7%; Hawaii, Maine, and California round out the top five in terms of COVID-19 impact.

Meanwhile, Congress is deadlocked over whether it should send more cash to states.

The researchers figure that a one percentage-point increase in employment translates to a 1.56% pp rise in tax revenue; they reverse-engineered the number using state unemployment-insurance claims as of June 5 to calculate the average 20% tax revenue impact of the pandemic.

The states or districts expected to experience revenue declines of 4% or less are Alaska; Washington, DC; and South Dakota.

ETFs: NAC, PZC, PCK, PCQ, NRK, BNY, NKX, NXJ

https://seekingalpha.com/news/3583114-covidminus-19-cuts-least-10-states-tax-revenue-30

Biotech week ahead, June 15

Biotech stocks came under pressure along with the broader market in the week ended June 12, as a worsening pandemic situation and its impact on the economy led to an across-the-board sell-off in the global markets.
The week kickstarted with the rumor of a big-ticket acquisition. AstraZeneca plc AZN 2.18% reportedly approached Gilead Sciences, Inc. GILD 0.52% with a bid, although experts and analysts shrugged off the possibility of a deal materializing.
The FDA promptly approved Viela Bio Inc’s VIE 3.65% drug for treating neuromyelitis optica spectrum disorder.
More importantly, five biopharma companies debuted on Wall Street, raising a combined $983.25 million. The week also witnessed virtual presentations at key conferences such as the European Hematology Association Congress.
Here are the key catalysts for the unfolding week.
Conferences

• The Endocrine Society’s ENDO Online 2020: June 8-22
• 25th Edition of the European Hematology Association, or EHA, Annual Congress held in virtual format: June 11-21
• American Academy of Dermatology, or AAD, Virtual Meeting Experience: June 12-14
• The American Diabetes Association, or ADA, 80th Scientific Sessions – Virtual: June 12-16
• The World Federation of Hemophilia, or WFH, Virtual Summit: June 14-19

PDUFA Dates

The FDA is scheduled to give its verdict on Merck & Co., Inc.’s MRK 2.92% Keytruda as a monotherapy option for unresectable or metastatic solid tumors, with tissue tumor mutational burden-high. (Tuesday)
Ultragenyx Pharmaceutical Inc RARE 0.47% and its Japanese partner Kyowa Kirin have a tryst with the FDA, as the agency is set to rule on hypophosphatemia treatment candidate burosumab. (Thursday)
The regulatory agency will also decide on Epizyme Inc’s EPZM 8.47% regulatory application for label expansion for tazemetostat, this time for follicular lymphoma. (Thursday)
Nabriva Therapeutics PLC – ADR NBRV 17.42% is knocking at the FDA altar for the second time for its investigational antibiotic contepo for treating complicated urinary tract infection. Late May, the company hinted at the decision being delayed due to the FDA requiring to inspect facilities of third-party manufacturers in Europe (Friday)
Evoke Pharma Inc EVOK 12.13% has a PDUFA date for its Gimoti to treat women with acute and recurrent diabetic gastroparesis. (Friday)

Adcom Meetings

FDA’s Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee will consider through teleconferencing the SP 2577 presentation by Salarius Pharmaceuticals Inc SLRX 15.36% and marizomib, presentation by Celgene, a subsidiary of Bristol-Myers Squibb Co BMY 2.84%. SP 2577 is being evaluated for the treatment of relapsed/refractory patients with Ewing sarcoma and marizomib for multiple myeloma.
The FDA said the subcommittee will consider and discuss issues relating to the development of each product for pediatric use and provide guidance to facilitate the formulation of written requests for pediatric studies, if appropriate.

Clinical Readouts/Presentations

ProQR Therapeutics N.V. PRQR 3.05% will make a virtual presentation of data from the Phase 1/2 trial of intravitreal sepofarsen, an antisense oligonucleotide, in Leber congenital amaurosis 10 due to p.Cys998X mutation in the CEP290 gene. The data is to be shared via a video presentation through the Association for Research in Vision and Ophthalmology. (available online from Monday)
Sanofi SA SNY 0.46% is scheduled to host a virtual scientific session to present data from the Phase 3 COMET trial of investigational enzyme replacement therapy avalglucosidase alfa in patients with late-onset Pompe disease. (Tuesday)
Catalyst Biosciences Inc CBIO 5.49% is due to present at the WFH virtual summit Phase 2a data for factor IX levels of a daily subcutaneous prophylaxis treatment regimen of dalcinonacog alfa in hemophilia B.

Earnings

• Centogene NV CNTG 0.52% (Monday, before the market open)
• BioNano Genomics Inc BNGO 2.71% (Thursday, after the close)
• Urovant Sciences Ltd UROV 0.36% (Thursday, after the close)

IPOs

Royalty Pharma, which buys royalties for late-stage and commercial drugs, has filed to offer 70 million shares in an initial public offering at an estimated price range of $25-$28. The company has applied for listing its shares on the Nasdaq under the ticker symbol RPRX.

IPO Quiet Period Expiry

Inari Medical Inc NARI 0.39%
https://www.benzinga.com/general/biotech/20/06/16244480/the-week-ahead-in-biotech-fda-decisions-in-the-cards-for-merck-epizyme-evoke-and-ultragenyx

Early Covid Vaccines Likely To Target Further Complications, Not Infection

Some of the earliest novel coronavirus (COVID-19) vaccines to be approved are more likely to target prevention against developing severe symptoms from catching the virus, rather than the initial infection, multiple health experts told Bloomberg.
Imperial College London professor Robin Shattock, who is working on developing the university’s COVID-19 vaccine, told Bloomberg that the earliest vaccines are likely to come with limitations.
“It’s quite possible a vaccine that only protects against severe disease would be very useful,” he said.
“Vaccines need to protect against disease, not necessarily infection,” Scripps Research immunologist and vaccine researcher Dennis Burton added, as reported by Bloomberg.
The Food and Drugs Administration spokesperson Michael Felberbaum also noted that the federal regulatory agency is willing to approve a vaccine, even if it works just against deadly symptoms.
“We would potentially consider an indication related to prevention of severe disease, provided available data support the benefits of vaccination,” Felberbaum told Bloomberg. “For licensure we would not require that a vaccine protects against infection.”
Governments across the globe are looking to restart economic activities as lockdowns imposed to curb the spread of the virus become infeasible to continue, without significantly hurting the domestic economies and employment.
A vaccine that works just against developing the severe disease will reduce the risk of death for some of the most vulnerable populations, including the elderly and those with underlying diseases.
“I would have liked to have had protection against infection,” the National Institute of Allergy and Infectious Diseases Director Anthony Fauci told Stat earlier this month.
“But then again, it depends on what you’re looking for with the vaccine. That vaccine doesn’t look like it’s a knockout for protecting against infection, but it might be really very good at protecting against disease,” Fauci said, referring to a vaccine candidate developed by AstraZeneca plc AZN 2.1% in partnership with Oxford University.
Several other vaccine candidates, including those of Moderna Inc. MRNA 5%, Inovio Pharmaceuticals Ltd. INO 7.14%, and Pfizer Inc. PFE 1.4%, are seeing clinical trials. Johnson & Johnson JNJ 0.95% is expected to begin the clinical trial of its vaccine later this month.
https://www.benzinga.com/news/20/06/16250455/early-coronavirus-vaccines-likely-to-target-further-complications-not-infection-health-experts-say

NYC COVID-19 Contact Tracers Not Asking About George Floyd Protest Participation

Over the two last weeks, Mayor Bill de Blasio and others have voiced concerns that packed police brutality protests across the city could trigger a new wave of COVID-19 infections.

Whether or not that’s the case, however, remains unknown — and de Blasio’s team won’t be directly trying to find out.

The hundreds of contact tracing workers hired by the city under de Blasio’s new “test and trace” campaign have been instructed not to ask anyone who’s tested positive for COVID-19 whether they recently attended a demonstration, City Hall confirmed to THE CITY.

“No person will be asked proactively if they attended a protest,” Avery Cohen, a spokesperson for de Blasio, wrote in an emailed response to questions by THE CITY.

Instead, test-and-trace workers ask COVID-positive individuals general questions to help them “recall ‘contacts’ and individuals they may have exposed,” Cohen said. Among the initial questions: “Do you live with anyone in your home?”

Tracers then ask about “close contacts” — defined as being within six feet of another person for at least 10 minutes.

It’s up to tested individuals to volunteer whether any of those close contacts occurred during protests. “If a person wants to proactively offer that information, there is an opportunity for them to do so,” Cohen wrote.

The mayor announced his “test and trace” program on May 8, promising that the city would hire 1,000 “contact tracers.” City Hall has declined to spell out how many individuals have been questioned so far, but de Blasio promised to release that information Monday.

Since the effort began, officials say most — but not all — people questioned by contact tracers have been cooperative. Some, however, have refused to volunteer any information about their close contacts.

“Naturally, we have not been able to obtain all information from all positive cases, but engagement among those reached is high,” Cohen wrote.

Mayor and Gov Want to Know

There’s no direct effort to resolve a question both de Blasio and Gov. Andrew Cuomo have asked repeatedly since the demonstrations against police brutality erupted following the death of George Floyd at the hands of Minneapolis police: Are the protests helping spread the virus?

“That’s the one variable in this equation that we’re not sure of: We don’t know what the effect of those protests are,” Cuomo said last week.

 

The three-day average percentage of New Yorkers whose COVID-19 test turned out positive has dropped dramatically, from 69% on March 31 to an all-time low of 2% as of June 8.

This has occurred, in part, because initially only people diagnosed as very sick were tested. More recently, a much larger pool of individuals has been tested — including those with no symptoms — driving down the percentage of positives.

But there’s a growing concern the numbers could spike again, given Phase One of the city’s reopening and the protests.

So far, there have been no apparent signs of a dramatic swing. De Blasio on Thursday announced the three-day average percentage of positive tests had risen slightly from 2% to 3%.

Cuomo and de Blasio find themselves walking a tightrope, warning protesters to be aware that COVID-19 remains a very real threat to life and strongly advising all who attend demonstrations to get tested. But they are also steering clear of dissuading anyone from participating in demonstrations.

A Different Experience

A key source of tests for the virus now is the medical chain CityMD with 100 clinics in the city, New Jersey and Long Island. A New Yorker who called up CityMD last week to get an appointment for a test after witnessing a daunting line at one of the clinics told THE CITY that the CityMD staff asked the individual whether they’d attended a protest.

CityMD officials did not respond to messages seeking comment.

In Nassau County, health officials take a slightly different approach. While they do not ask individuals who test positive whether they’ve attended protests, they do ask them where they’ve been recently.

 

“We ask them questions about where they’ve been so that we can gauge who may be at risk,” said Mary Ellen Laurain, a spokesperson for the Nassau County Health Department. “It may come out as part of the interview, but we ask more open-ended questions.”

Despite Cuomo’s concerns about the effect of the protests, the state Health Department has remained neutral on the issue.

Jonah Bruno, an agency spokesperson, stated, “We’re working with New York City to balance the public health priority while also protecting personal privacy, as we seek to ensure a thorough contact tracing program that helps us contain the COVID-19 virus and monitor any fluctuations in the infection rate as we continue reopening New York.”

‘Treat People with Ease’

Dr. S. Patrick Kachur, a professor at Columbia University Mailman School of Public Health and a former official at the Centers for Disease Control and Prevention, said contact trackers face a balancing act: trying to obtain useful information about an infected person’s contacts without alienating them with overly intrusive questions.

Asking someone if they’d been at a protest could wind up discouraging them from being candid in their answers, he noted.

“I think the logic has to do with the fact that contact tracing requires a strong level of trust between the interviewer and the person they’re talking to,” he said. “It’s really important to have a good rapport and treat people with ease. It’s important to not ask questions that will impede your ability to do the best job you can.”

For example, Kachur, who has been involved in contact tracking during previous pandemics involving the flu and Zika, noted that when investigators are trying to track the spread of HIV, tuberculosis or most diseases, they make a point of not asking about a person’s immigration status.

‘It would be really challenging to trace those you’ve been protesting with.’

And while knowledge of how the protests might be sparking a second wave would be helpful, it would be very difficult to track close contacts at events attended by thousands of strangers, he said.

“There’s definitely a concern that state and city officials have that the protests could be a place where transmission occurs, but that risk is lower than household and other community contacts,” Kachur said. “And it would be really challenging to trace those contacts who you’ve been protesting with.”

Going forward, a key question will be whether Blasio’s test-and-trace program can handle the workload as increased testing yields more positive cases and more contacts to trace.

“How well are they able to keep up with the complete investigations that they are able to trace?” Kachur asked. “If they have more cases than they can deal with, that would be concerning. It would be a confusing month or two here.”

https://www.thecity.nyc/coronavirus/2020/6/14/21290963/nyc-covid-19-trackers-skipping-floyd-protest-questions-even-amid-fears-of-new-wave