Bristol Myers pays $650M for rights to Eisai's phase 1 antibody-drug

 Bristol Myers Squibb is paying $650 million to secure rights to Eisai’s folate receptor alpha-targeted antibody-drug conjugate (ADC) MORAb-202. The deal, which is worth up to $2.5 billion in milestones, sets Bristol Myers up to work with Eisai to get the drug into a registrational study next year.

Eisai created MORAb-202 by pairing an anti-folate receptor alpha (FRα) antibody with its anticancer agent eribulin. The idea is to use overexpression of the receptor in various malignancies to facilitate the targeted delivery of a therapeutic payload. The same concept underpins other ADCs such as Sutro’s STRO-002 and ImmunoGen’s once-failed phase 3 prospect mirvetuximab soravtansine.

Bristol Myers sees enough promise in MORAb-202 to bet big. Eisai is receiving $200 million to cover its R&D expenses and a further $450 million upfront payment, plus the promise of major milestones and royalties. In return, Bristol Myers has secured the right to jointly develop and commercialize the ADC with Eisai in North America, Europe, Russia, Japan, China and a clutch of other countries in the Asia Pacific region. Bristol Myers is solely responsible for MORAb-202 in the rest of the world. 

Eisai landed the deal after reporting data from a phase 1 clinical trial in 22 patients with FRα-positive solid tumors who failed to respond to standard therapy. After administering MORAb-202 at doses of 0.3 to 1.2 mg/kg once every three weeks, investigators saw one complete response and nine partial responses. Eight patients had stable disease. 

Japan’s Eisai is running that study in its home country while testing MORAb-202 in a separate phase 1/2 clinical trial in the U.S. Based on the evidence generated so far, Bristol Myers and Eisai are set to enter the registrational stage of development as early as next year. The partners are yet to disclose the target indications for the registrational work. FRα is overexpressed in cancers of the ovary, lung, breast and other organs. 

Other developers of FRα-targeted ADCs have identified opportunities to use their drug candidates in combination with checkpoint inhibitors such as Bristol Myers’ Opdivo. Sutro shared preclinical data on such a combination last year, while ImmunoGen’s mirvetuximab soravtansine is being studied in endometrial cancer patients in combination with Merck’s Keytruda. 

https://www.fiercebiotech.com/biotech/bristol-myers-pays-650m-for-rights-to-eisai-s-phase-1-adc

Low Dosage May Be Behind Low Efficacy of CureVac Vaccine

  The low dosage might be a key reason why CureVac's COVID-19 vaccine reported disappointing efficacy in a pivotal late-stage trial, the scientist leading the study of the shot said on Thursday.

The German biotech's vaccine proved only 47% effective in an initial trial, far lower than those of rivals BioNTech/Pfizer and Moderna, which are also based on mRNA technology and had efficacy rates well above 90%.

Peter Kremsner from the University Hospital in Tuebingen which is running the trial told Reuters the low efficacy is "very likely due to the dose".

Unlike BioNTech and Moderna, CureVac did not modify the mRNA used in shot and therefore a higher dosage was not possible because of the side effects to be expected, Kremsner said.

With just 12 micrograms of mRNA per dose, the company has been seeking to position itself as a low-dose alternative to BioNTech and Moderna's established shots with 30 and 100 micrograms per shot, respectively.

It is also easy to store and cheaper than the other mRNA shots too. The European Union has agreed to pay 12 euro ($14.32) per dose for supplies of the shot, an EU internal document shows, but has paid more than 15 euros for the other mRNA shots. However, the interim trial analysis goes some way to challenging the expectation, which was previously reflected in the company's share price, that all mRNA vaccines are similar. The news wiped as much as 52% off the company's value on Thursday.

CureVac said on Wednesday that new variants had proved a headwind, but data from BioNTech and Moderna have, however, so far suggested only somewhat weaker protection against new variants.

Kremsner said he thought it was probably a "long shot" as to whether CureVac's vaccine might turn out to be more effective when targeting a particular variant.

The disappointing results are a blow since European governments had been hoping to add it to their arsenal after age limits were imposed on the use of the Johnson & Johnson and AstraZeneca vaccines due to a link to extremely rare but potentially fatal clotting disorder.

https://www.usnews.com/news/top-news/articles/2021-06-17/low-dosage-may-be-behind-low-efficacy-of-curevac-vaccine-study-leader

India 'Should Brace for Third COVID-19 Wave by October'

 A third wave of coronavirus infections is likely to hit India by October, and although it will be better controlled than the latest outbreak the pandemic will remain a public health threat for at least another year, according to a Reuters poll of medical experts.

The June 3-17 snap survey of 40 healthcare specialists, doctors, scientists, virologists, epidemiologists and professors from around the world showed a significant pickup in vaccinations will likely provide some cover to a fresh outbreak.

Of those who ventured a prediction, over 85% of respondents, or 21 of 24, said the next wave will hit by October, including three who forecast it as early as August and 12 in September. The remaining three said between November and February.

But over 70% of experts, or 24 of 34, said any new outbreak would be better controlled compared with the current one, which has been far more devastating - with shortage of vaccines, medicines, oxygen and hospital beds - than the smaller first surge in infections last year.

"It will be more controlled, as cases will be much less because more vaccinations would have been rolled out and there would be some degree of natural immunity from the second-wave," said Dr Randeep Guleria, director at All India Institute Of Medical Sciences (AIIMS).

Graphic - Will India suffer a third wave of COVID-19?: https://fingfx.thomsonreuters.com/gfx/polling/xlbvgkeybvq/Reuters%20Poll-%20Possibility%20of%20Covid-19%20third%20wave.PNG

So far, India has only fully vaccinated about 5% of its estimated 950 million eligible population, leaving many millions vulnerable to infections and deaths.

While a majority of healthcare experts predicted the vaccination drive would pick up significantly this year, they cautioned against an early removal of restrictions, as some states have done.

When asked if children and those under 18 years would be most at risk in a potential third wave, nearly two-thirds of experts, or 26 of 40, said yes.

"The reason being they are a completely virgin population in terms of vaccination because currently there is no vaccine available for them," said Dr Pradeep Banandur, head of epidemiology department at National Institute of Mental Health and Neurosciences (NIMHANS).

Experts warn the situation could become severe.

"If children get infected in large numbers and we are not prepared, there is nothing you can do at the last minute," said Dr Devi Shetty, a cardiologist at Narayana Health and an advisor to the Karnataka state government on pandemic response planning.

"It will be a whole different problem as the country has very, very few paediatric intensive care unit beds, and that is going to be a disaster."

But 14 experts said children were not at risk.

Earlier this week, a senior health ministry official said children were vulnerable and susceptible to infections but that analysis has shown a less severe health impact.

Graphic - What will happen to India's vaccination drive?: https://fingfx.thomsonreuters.com/gfx/polling/xklpyaylmpg/Reuters%20Poll-%20India%20Covid-19%20outlook.PNG

While 25 of 38 respondents said future coronavirus variants would not make existing vaccines ineffective, in response to a separate question, 30 of 41 experts said the coronavirus will remain a public health threat in India for at least a year.

Eleven experts said the threat would remain for under a year, 15 said for under two years, while 13 said over two years and two said the risks will never go away.

"COVID-19 is a solvable problem, as obviously it was easy to get a solvable vaccine. In two years, India likely will develop herd immunity through vaccine and exposure of the disease," said Robert Gallo, director of the Institute of Human Virology at the University of Maryland and international scientific advisor, Global Virus Network.

https://www.usnews.com/news/world/articles/2021-06-18/india-should-brace-for-third-covid-19-wave-by-oct-say-health-experts-reuters-poll

Health experts warn of Olympic COVID-19 threat, prefer no spectators

 Japan's top medical experts warned on Friday that holding the Olympics during the COVID-19 pandemic could increase infections, and said banning all spectators was the least risky option, setting up a possible collision with organisers.

The report, led by top health adviser Shigeru Omi, was released after Tokyo 2020's organising committee chief told the Sankei newspaper she wanted to allow up to 10,000 spectators at stadiums for the global sport extravaganza, which kicks off on July 23.

Japan is pushing ahead with hosting the multi-billion-dollar delayed Games despite worries about another surge in COVID-19 infections and strong public opposition, although organisers have banned spectators from overseas.

Cancellation of the event - originally meant to showcase a revitalised nation after decades of doldrums - would be costly for organisers, the Tokyo government, sponsors and insurers.

"This event is different from ordinary sports events in scale and social interest and because it overlaps with summer vacations ... there is a risk the movement of people and opportunities to interact during the Olympics will spread infections and strain the medical system," the experts said. "Holding with Games without spectators is the least risky option and we think desirable."

A final decision on domestic spectators will be made at a meeting to be held as early as Monday among Tokyo 2020 organisers, the International Olympic Committee, International Paralympic Committee, Japanese government and Tokyo Metropolitan government.

"I would like it to be held with spectators. I plan to head into the five-way meeting with that in mind," the Sankei newspaper quoted Tokyo 2020 head Seiko Hashimoto as saying in an interview published late on Thursday.

Hashimoto said the advice from Omi would inform talks among the IOC and others.

https://uk.sports.yahoo.com/news/japan-health-experts-warn-olympics-050252727.html

Britain reports steep rise in weekly Delta variant cases

 Britain has reported another steep rise in the weekly reported cases of the Delta coronavirus variant, Public Health England data showed on Friday, after Prime Minister Boris Johnson decided to delay the final lifting of lockdown restrictions.

PHE said there had been 33,630 new cases of the Delta variant first identified in India in the week to June 16, taking the number of confirmed cases to 75,953, a 79% increase on the previous total.

"Cases are rising rapidly across the country and the Delta variant is now dominant," said Jenny Harries, Chief Executive, UK Health Security Agency.

"It is encouraging to see that hospitalisations and deaths are not rising at the same rate but we will continue to monitor it closely."

The Delta variant now comprises 91% of sequenced cases, Public Health England said. Using most recent data which includes genotyped data which has more rapid turnaround times, 99% of cases were estimated to be Delta.

In response to the surge in cases of Delta, Johnson is aiming to accelerate vaccination plans to give every adult a first COVID-19 vaccine by July 19, the new date at which he plans to end COVID restrictions in England.

On Friday, COVID-19 vaccinations were opened up to all people over 18 in England.

PHE added that vaccines were still effective at providing protection against risk of hospitalisation from the Delta variant.

It said that as of June 14, a total of 806 people had been hospitalised with the Delta variant, an increase of 423 from the previous week.

PHE added that of those hospitalised, 527 were unvaccinated, and 84 had received both doses.

https://news.trust.org/item/20210618080448-erwz3

S.Korea to mix-and-match COVID-19 vaccine doses for 760,000

 Some 760,000 South Koreans who have received a first dose of AstraZeneca Plc's COVID-19 vaccine will be offered Pfizer Inc's vaccine as a second shot due to shipment delays by global vaccine sharing scheme COVAX, the government said.

Several countries, including Canada and Spain, have already approved such dose-mixing mainly due to concerns about rare and potentially fatal blood clots linked to the AstraZeneca vaccine.

A Spanish study found that giving a dose of the Pfizer shot to people who already received the AstraZeneca vaccine is highly safe and effective, according to preliminary results.

Some 835,000 doses of the AstraZeneca's vaccine from COVAX were scheduled to arrive by the end of June, which South Korea planned to use mainly as a second shot for around 760,000 health and frontline workers who had received their first dose in April.

The shipment is delayed to July or later, while the country had used up available AstraZeneca reserves to meet stronger than expected participation in its vaccination campaign which helped the country meet its first-half inoculation target ahead of schedule.

Over 27% of its 52 million population have been inoculated with at least one dose of a coronavirus vaccine as of Thursday, and the country is on track to meet a target of 70% by September and reach herd immunity before November.

The government expects to receive 80 million doses of COVID-19 vaccines in the third quarter including 10 million in July. They are from AstraZeneca, Pfizer, Johnson & Johnson and Moderna.

South Korea said last month it will conduct a clinical trial that mixes COVID-19 doses from AstraZeneca with those from Pfizer and others.

It has so far run a trial in 100 health workers to examine the formation of antibody and other immune effects, Korea Disease Control and Prevention Agency (KDCA) director Jeong Eun-kyeong told a briefing on Thursday.

South Korea reported 507 new infections by midnight on Thursday, for a tally of 150,238 cases, the KDCA said, with a death toll of 1,996 since the pandemic began.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-nbsp-S-Korea-to-mix-and-match-COVID-19-vaccine-doses-for-760-000-people-35640572/

BioNTech: 1st Patient Dosed in Phase 2 Trial of mRNA-based BNT111 in Advanced Melanoma

 -- First program from BioNTech's fully-owned mRNA cancer vaccine platform

      FixVac treats patients in a randomized clinical Phase 2 clinical trial 
 
   -- Phase 2 trial is based on positive results from Phase 1 Lipo-MERIT trial 
      that demonstrated a favorable safety profile for BNT111 as well as 
      durable objective responses observed in patients with melanoma who had 
      progressed following prior checkpoint blockade 
 
   -- Trial is enrolling a total of 120 patients at clinical trial sites in the 
      European Union, the United Kingdom, the United States and Australia 

https://www.marketscreener.com/quote/stock/BIONTECH-SE-66771992/news/Press-Release-nbsp-BioNTech-Announces-First-Patient-Dosed-in-Phase-2-Clinical-Trial-of-mRNA-based-35641251/