Clinical Trials of Nasal COVID Vaccine to Start This Year

 A protein-based vaccine for COVID-19 administered through the nose has been developed by the BioMAP team at the French National Research Institute for Agriculture, Food, and Environment (INRAE)–University of Tours Infectious Diseases and Public Health (ISP) joint research unit. This vaccine can trigger an immune response at the systemic level, similar to traditional intramuscular vaccines, as well as at the mucosal level.

"Instillation in the nose induces an immune response in the nasal cavities. Because of this, we're able to stop the virus very early on. This means it will no longer be able to multiply and infect the people around you," explained Isabelle Dimier-Poisson, PhD, an expert in the immunology of infectious diseases at the University of Tours, and incoming general and research manager at LoValTech, a start-up that will lead development of the vaccine formulation. "Intramuscular vaccines protect against severe forms of COVID. However, if you catch the virus, you could infect others. The intranasal vaccine does away with this problem," she explained.

Like traditional vaccines, the intranasal vaccine is effective against serious forms of COVID-19. And in addition to being able to stop the virus early in the nasal cavities, it has several other advantages: "All of the current COVID-19 vaccines on the market are based on the spike protein, which then mutated, rendering those vaccines less effective. Our vaccine contains not only the spike protein, but other proteins that do not mutate and are found in all variants. The vaccine can be stored at 39 °F (~4 °C), but survives at room temperature, which makes it ideal for countries where meeting cold-chain requirements can be a challenge," said Dimier-Poisson. Another plus is that administration of this vaccine is noninvasive, which can make the immunization procedure less stressful for people, especially children.

A Very Strong Systemic and Mucosal Immune Response

The team filed a patent application for the intranasal vaccine in September 2021. The researchers are currently completing preclinical trials, and results so far have been promising. "A very strong systemic and nasal mucosal immune response was induced" when researchers delivered two nasal immunizations, 3 weeks apart, in a mouse model, she reported.

But can the vaccine protect against serious forms of COVID-19? Using mice that had been genetically modified to be susceptible to SARS-CoV-2, the researchers administered two doses of the vaccine one group; the mice in the control group received nothing. When they then infected the mice with the virus, all the vaccinated mice survived and developed no symptoms (no respiratory distress, no weight loss, etc.), whereas the mice in the control group all exhibited symptoms of respiratory distress.

To assess how well the vaccine prevented transmission of the virus, the researchers administered two doses of the vaccine, 3 weeks apart, to hamsters. "The hamsters showed no viral load in the lungs," said Dimier-Poisson.

To determine the vaccine's effectiveness against COVID-19 variants, the team conducted in vitro and in vivo studies. "We were able to show the vaccine's efficacy against Beta and Delta. We're currently finalizing tests on Omicron," she said.

So far there have been no adverse effects. "This is a protein-based vaccine without adjuvant. It's totally safe. We fully expect that it'll be used for children and immunocompromised patients," Dimier-Poisson explained.

The production phase of Good Manufacturing Practice got underway thanks to efforts that raised close to €3 million (~US$3.4 million), which includes €1.5 million (~US$1.7  million) from the Ministry of Higher Education, Research, and Innovation (MESRI), and €900,000 (US$1.3  million) from ANRS | Emerging Infectious Diseases.

"We've embarked on a creative biotech process to continue developing the vaccine," said Dimier-Poisson, who noted that "we'll still need a substantial amount of money to carry on with that development." The team plans to start the first clinical trial before the end of 2022, and hopes that the vaccine will be on the market by 2024.

"Even if the pandemic ends, the virus will still be around as an epidemic. People who got an intramuscular vaccine will be able to take our nasal vaccine to prevent them from transmitting the virus. Our vaccine will also be directed at the many people around the world who are not yet immunized. We're committed to making a vaccine available to these populations at cost," stated Dimier-Poisson, who believes that "the vaccine will be of interest to everyone, whether as an initial immunization or as a booster."

Not many vaccines are administered through the nose; the World Health Organization lists only six. "We're the only ones in France who are developing this type of vaccine," said Dimier-Poisson. "It's a message of hope that we'll all get back to the way life was before COVID."

https://www.medscape.com/viewarticle/967753

Threats to the CD20 space – and Biogen's cash cow

Biogen has collected billions in royalties from Roche’s anti-CD20 franchise, and will continue to do so after opting in to a bispecific project this week. But what are the threats to this income stream, and for how much longer can Roche expect to dominate this space? Consensus forecasts from Evaluate Pharma show why Biogen decided to claim its rights over mosunetuzumab. The project is attracting the highest sales forecasts among the next-generation CD20 approaches, though there are many contenders in the pipeline and lots of data still to come. Abbvie this week said it hoped to file the Genmab-derived epcoritamab for accelerated approval later this year, for example, putting it not too far behind Roche, which has started a rolling submission for mosunetuzumab. Elsewhere, biosimilar versions of Rituxan are already biting; the market share of products from Pfizer and Teva/Celltrion are not too far off Rituxan's slice of the US market. Ocrevus is making up those losses for now, and the MAb is unlikely to see low-cost competition this decade. But Roche will be highly motivated to ensure that CD20 bispecifics prolong its stranglehold on this space, a determination from which Biogen looks well set to benefit.

https://www.evaluate.com/vantage/articles/news/deals-snippets/threats-cd20-space-and-biogens-cash-cow

A year of Tigit (and Alzheimer’s) for Roche

 Two years after kicking off Tigit mania with the start of nine pivotal studies of its contender, tiragolumab, Roche will find out whether its bet has been worth it. 2022 will be the year that four of these studies yield data, the Swiss company told investors today.

This will be an important theme to watch as many investors focus instead on Alzheimer’s disease, and the impending phase 3 readouts of gantenerumab’s Graduate-1 and 2 trials. But it is clear that Roche is not taking its foot off the Tigit pedal, despite phase 2 studies indicating tiragolumab’s potential lying mainly in PD-L1-high lung cancer.

As such the big question will be whether tiragolumab’s huge pivotal programme suggests significant activity in any of the other tumour types Roche highlighted at today’s fourth-quarter presentation. In terms of 2022 catalysts these comprise second-line cervical, and front-line SCLC and oesophageal cancers, in addition to PD-L1-high first-line NSCLC.

Tiragolumab's 2022 pivotal readouts
Study	Setting	Design	Primary endpoints	Enrolment completed (n)
Phase 3
Skyscraper-02	1L SCLC	Tecentriq + chemo combo, vs Tecentriq + chemo	PFS & OS	Q1 2021 (470)
Skyscraper-01	1L PD-L1 "high" NSCLC	Tecentriq combo, vs Tecentriq	PFS & OS	Q3 2021 (500-600)
Skyscraper-08	1L oesophageal cancer	Tecentriq + chemo combo	PFS & OS	Q4 2021 (500)
Pivotal phase 2
Skyscraper-04	2L PD-L1+ve cervical cancer	Tecentriq combo, vs Tecentriq	ORR*	Still enrolling (172)
Note: *OS is a secondary endpoint. Source: Roche & clinicaltrials.gov.

Based on recent events, cervical cancer at least looks like a long shot. The quick front-line approval and formal second-line label for Merck & Co’s Keytruda, based on controlled studies showing a survival benefit, have already claimed the scalp of Agenus’s balstilimab.

Balstilimab’s filing was based on remission rates in an uncontrolled study, and it is clear that only survival data will now do. Tiragolumab’s Skyscraper-04 trial, a Tecentriq combo in second-line, PD-L1-positive disease, primarily tests ORR, with OS a secondary endpoint.

Apart from the primary focus on ORR, it is not clear whether Tecentriq, a drug not approved for cervical cancer, will now be deemed an appropriate comparator in this setting. A further indication of how competitive this cancer is is Sanofi/Regeneron’s recent withdrawal of a second-line Libtayo filing – backed by an OS benefit versus chemo, not Keytruda.

Still, the main tiragolumab catalyst remains Skyscraper-01, in PD-L1-high first-line NSCLC, as a Tecentriq combo. The phase 2 Cityscape trial had shown a 77% reduction in risk of death versus Tecentriq in PD-L1 ≥50% expressers, a benefit Roche today reminded investors was “eye-popping”. Skyscraper-01 is much bigger than Cityscape, so only the most aggressive bulls expect such a result to be repeated.

Of the other two pivotal readouts, in SCLC tiragolumab plus Tecentriq and chemo will aim to outdo the Tecentriq chemo combo in its approved use, though no clinical data for tiragolumab have ever been reported in this cancer. A hit in oesophageal cancer would represent a new setting for tiragolumab and Tecentriq alike.

In and out

Roche’s fourth-quarter update also included news of an unusually large number of new molecular entities entering the clinic for the first time, as well as numerous phase 1 and 2 discontinuations.

The existence of many of those in the former category has barely been disclosed before, so their mechanisms remain unknown, though two new Chugai projects, SPYK04 and LUNA18, appear to target the Ras/Map kinase pathway.

An intriguing Alzheimer’s asset, RG6289, is also new to phase 1. Its mechanism is undisclosed, and it is distinct from RG6035, the brain-shuttle version of gantenerumab that has been in phase 2 since early 2021.

These and other assets will remain closely watched, but as far as 2022 catalysts go gantenerumab’s readout is the “biggest one of all”, Bill Anderson, head of Roche’s pharma business, told investors.

Roche assets moving into the clinic, and moving out of development
Project	Mechanism	Trial	Indication
Newly into clinical trials…
RG6129 / RO7444973	HLA-A*02 Mage-A4 T-cell engager	NCT05129280	Mage-A4+ve solid tumours
RG6289	?	?	Alzheimer's disease
RG6341 / GDC-6599	?	?	Asthma
RG6392 / RO7497987	?	ISRCTN92655801	Cancer
RG6501 / OpRegen*	RPE cell therapy	?	Geographic atrophy
LUNA18	Ras inhibitor	NCT05012618	Ras+ve solid tumours
SPYK04	Undisclosed small molecule	NCT04511845	Tumours with Map kinase pathway alterations (eg, Braf/Ras+ve)
…and discontinued
RG6232 / RO7293583	Anti-Tyrp1 T-cell engager	NCT04551352 (ph1)	Tyrp1+ve melanomas
PCO371	PTH1 receptor antagonist	NCT04209179 (ph1 stopped for poor risk/benefit)	Hypoparathyroidism
RG7835 / RO7049665	IgG Fc-IL-2 mutein fusion protein	NCT04790916 (ph2 stopped for lack of efficacy)	Autoimmune hepatitis
RG7992 / RO7040551 / BFKB8488A	Anti-FGFR 1 & Klotho beta MAb	NCT04171765 (ph2)	Nash
RG6367 / SPK 7001	REP 1 gene therapy	NCT02341807 (ph2)	Choroideraemia
Note: *licensed from Lineage Cell Therapeutics. Source: Roche, Chugai, clinicaltrials.gov & Evaluate Pharma. https://www.evaluate.com/vantage/articles/news/corporate-strategy/year-tigit-and-alzheimers-roche

Lilly pushes back timeline for Alzheimer's drug application

 Eli Lilly and Co deferred its timeline to complete application for accelerated approval of its experimental Alzheimer's drug, saying it expects such an approval to make little difference with Medicare's limited coverage terms.

Shares of Eli Lilly fell 2.6% to $244.21 on Thursday, after the drugmaker said it would complete the application sometime later in 2022, pushing away from first quarter, its initial timeline.

The U.S. Centers for Medicaid and Medicare Services has restricted coverage for Alzheimer's drugs, including Biogen's controversial treatment Aduhelm, only to patients taking part in approved clinical trials.

The agency's final coverage terms, due in April, are expected to apply to all drugs in the class, including Lilly's donanemab as well as those being developed by Roche Holding AG and Eisai Co Ltd.

"We're trying to take investor focus off the exact timing of accelerated approval, given our very limited expectations for the impact of that accelerated approval commercially," said Lilly's Chief Scientific Officer Daniel Skovronsky.

Skovronsky said the company expects data from the confirmatory trial of donanemab by mid-2023, after which it may have more clarity on reimbursements under Medicare.

"I think people are now expecting that there will probably be no sales for donanemab this year, and essentially zero sales next year," Mizuho Securities analyst Vamil Diwan said.

Lilly said a U.S. Food and Drug Administration decision on using its arthritis drug, Olumiant, in hospitalized COVID-19 patients is expected by the middle of this year.

The drug is currently authorized in the United States for treating hospitalized COVID-19 patients and saw a 59% jump in sales in the fourth quarter.

Lilly beat estimates for fourth-quarter revenue and profit, buoyed by strong demand for its top-selling diabetes drug Trulicity as well as higher sales of its COVID-19 antibody therapies.

https://finance.yahoo.com/news/1-eli-lilly-profit-beats-114855803.html

Pardes Biosciences IND Application for SARS-CoV-2 Treatment Cleared By FDA

 Pardes Biosciences Inc. said its investigational new drug application for PBI-0451, a candidate for the treatment and prevention of SARS-CoV-2 infections and associated diseases, has been cleared by the U.S. Food and Drug Administration.

The company said the clearance allows it to proceed with the initiation of additional Phase 1 clinical trials for PBI-0451 in the U.S.

Pending additional engagement with FDA and other regulators, the company sees beginning its global Phase 2/3 studies of PBI-0451 in SARS-CoV-2 infected patients in mid-2022.

PB-0451 is currently under evaluation in a Phase 1 placebo-controlled, blinded, randomized, dose escalation study in healthy volunteers in New Zealand evaluating the safety, tolerability, and pharmacokinetics of PBI-0451 after single and multiple ascending doses.

https://www.marketscreener.com/quote/stock/PARDES-BIOSCIENCES-INC-131203376/news/Pardes-Biosciences-IND-Application-for-SARS-CoV-2-Treatment-Cleared-By-FDA-37733770/

Amgen, Plexium to Collaborate on Targeted Protein Degradation Therapies

 Amgen Inc. on Thursday said it signed an exclusive multi-year research collaboration and license agreement with privately-held Plexium Inc. to identify novel targeted protein degradation therapies.

The Thousand Oaks, Calif., biotechnology company said the work will pair its early discovery expertise with Plexium's targeted protein degradation platform to develop new therapeutic agents in cancer and other serious diseases.

Amgen said the collaboration will initially focus on two programs, with options to add more. The company said Plexium is eligible to receive more than $500 million in milestone payments, along with royalties on product sales, if all options are exercised.

Amgen said it will have a commercial license to each program that advances to a predefined preclinical stage of development and will be responsible for global development and commercialization.

https://www.marketscreener.com/quote/stock/AMGEN-INC-4847/news/Amgen-Plexium-to-Collaborate-on-Targeted-Protein-Degradation-Therapies-37737320/

Britain gets fifth COVID vaccine after Novavax approval

 Britain on Thursday approved Novavax's two-dose COVID-19 vaccine for use in adults, bringing a fifth coronavirus shot to the country amid the rapid spread of the Omicron variant that has led to a spike in cases.

The vaccine, Nuvaxovid, was approved for use in Britons aged 18 years and older as it met the required safety, quality and effectiveness standards, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) said https://www.gov.uk/government/news/novavax-covid-19-vaccine-nuvaxovid-approved-by-mhra in a statement.

The British approval comes days after the drugmaker filed for U.S. authorization https://www.reuters.com/world/us/novavax-files-us-authorization-covid-19-vaccine-2022-01-31 of the vaccine following months of struggles with development and manufacturing problems, and follows a European approval in December which was also delayed.

The first shots, which will be made by Serum Institute of India, will not be shipped until March, Silvia Taylor, head of corporate affairs at Novavax, said in a briefing.

She did not give details on volumes.

British authorities and Novavax had in 2020 agreed https://www.reuters.com/article/us-health-coronavirus-novavax-britain-idUSKCN25A0HG to a supply of 60 million doses of the shot, while also agreeing to collaborate on late-stage trials for the vaccine in the country.

The U.S. company started shipping doses to the European Union in January, with 27 million expected to arrive in the first quarter and 42 million in the second, Taylor said.

Novavax's Nasdaq-listed shares were 0.7% lower at 1608 GMT.

Its vaccine in June was found to be more than 90% effective in a U.S. trial against a variety of variants, including Delta, while early data from December also suggested it would work against the Omicron variant.

"It is great to see our ... medicines regulator approve another COVID-19 vaccine. ... The next step will be for the independent Joint Committee on Immunisation and Vaccination to consider its use as part of the UK COVID-19 vaccination program," Health Secretary Sajid Javid said in a statement.

Novavax's protein-based vaccine uses a different technology from currently approved vaccines and gives Britain another option. Protein-based vaccines have been used for many years to prevent illnesses, including Hepatitis B.

"We suspect that those who haven't been vaccinated yet may be now more inclined to be vaccinated (with a traditional vaccine such as Novavax's)," said Paul Heath, leader of the UK trial and professor of pediatric infectious diseases at the University of London.

"There will ultimately be a role for this (vaccine) as a booster," he said. The shot has not been approved as a booster.

"We are continuing our vital safety work in monitoring the use of all COVID-19 vaccines, to ensure that their benefits in protecting people against COVID-19 disease continue to outweigh any risks," MHRA Chief Executive June Raine said.

Vaccines from AstraZeneca-Oxford, Pfizer-BioNTech , Moderna and Johnson & Johnson have already been approved for use in Britain.

The country currently has the seventh-highest tally of COVID-19 cases, according to Reuters, and government data showed it reported 88,171 new cases on Thursday https://www.reuters.com/world/uk/uk-records-new-88171-covid-cases-303-deaths-2022-02-03.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/Britain-gets-fifth-COVID-vaccine-after-Novavax-approval-37732465/