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Monday, September 7, 2020

Big pharma spinouts grow up

Companies formed around unwanted big pharma assets have a mixed record, although some parents are better at finding spinouts than others.

The approval of Viela Bio’s Uplizna earlier this year represented swift progress for a company that was only founded in 2018. It also marked another successful transition on to the market for an Astrazeneca spinout – of the three companies that the pharma giant has actively set on an independent path, another has seen a drug approved, and the third is in late-stage trials.

These other companies are Albireo and Entasis, and this track record arguably makes Astra one of the more successful big pharma companies when it comes to building new homes for unwanted assets. An Evaluate Vantage review of this activity finds that Merck KGaA is by far the most enthusiastic spinner, having forged nine young start-ups in the last decade, though not all of these are still around today.

Back in 2012 Merck KGaA’s biotech unit, Merck Serono, pledged to seed a number of companies after dramatically cutting back and reshaping its R&D operations in Geneva. This lead to a string of spinouts, including Asceneuron, Calypso Biotech and iOnctura, which remain early-stage companies. Tocopherx appears no longer to exist, although Prexton, the first to be spun out, was acquired by Lundbeck in 2018, for $123m up front.

A summary of spinouts from major drug developers
Parent company No. of spinouts Summary of progress
Merck KGaA9Two acquired, one listed and one product to market; two bankrupt
Pfizer6Three to market, three listed, one acquired; one bankrupt
Novartis3One acquired, two to market
Glaxozmithkline3One acquired, one in phase III; one bankrupt
Roche3Two acquired, two listed, one product to market 
Astrazeneca3All three listed, two to market, one in phase III
Sanofi2Both acquired while private
Johnson & Johnson2One to market and acquired; one bankrupt
Bayer2One acquired; one to market 
Takeda2Both still private, one in phase II
Eli Lilly2Both bankrupt
Teva Pharmaceutical Industries2Both bankrupt
Source: EvaluatePharma. 

Defining a spinout has become slightly more complicated with the emergence of motivated venture firms that actively seek unwanted projects and set out to build companies around them. A decade ago this activity was very much driven by the parent pharma company, which provided the assets and frequently staff, although external partners were generally brought on to provide financing.

For example, Bing Yao, chief executive of Viela, was head of respiratory, inflammation and autoimmunity at Astrazeneca’s Medimmune unit before striking out to head the start-up alongside several other Astra staffers; external investors initially injected $250m but Astra retained a large stake. Similar models were used with the spinouts of Albireo and Entasis.

Compare this to a start-up like Impact Biomedicines, which was set up around fedratinib, an asset that had been abandoned by Sanofi. The company was explicitly set up to buy the Jak2 inhibitor off the pharma giant, and was aided in large part by Medicxi, a venture firm and a big proponent of a so-called “asset-centric” investment model.

Sanofi retained a stake in Impact but the formation of that company was driven by parties external to the pharma giant. There are grey areas of course and to a certain extent this comes down to semantics – take Corvidia Therapeutics for example, which was recently bought by Novo Nordisk for $725m up front.

The company was founded by venture firms Sofinnova and Apple Tree, which funded a licensing deal over an Astrazeneca project that was earmarked for selling on. True, Corvidia also took several former Astra employees; however, the pharma giant does not consider Corvidia a spinout, under strict definitions of the term.

Track record

This overview focuses on spinouts that, as far as can be determined, were driven by the parent company, and focuses on those set up by very large drug developers only. It also only concerns spinouts of research-stage companies, and not the separation of business units with products already on the market.

Vantage’s search of EvaluatePharma’s database found 39 such companies that had been set on an independent path, most of which were formed in the past decade, spun out of 12 global drug makers.

Of these, nine are either bankrupt or no longer appear to be active; 27 remain privately owned while 13 moved on to the stock market. 11 have been acquired and 11 managed to get a product to market.

That around a quarter of these companies managed to cross the regulatory finish line is pretty impressive, given that many were set up with very early projects. Perhaps, though, this is not so surprising: a motivated parent is unlikely to spend the time and money to set up a new company unless it sees real potential.

Still, this does not necessarily mean that investors should rush to back big pharma spinouts. Nine have got to market but few have been real commercial success stories. The most notable spinouts are listed below, and even here several have taken years to deliver these achievements.

With venture firms flush with cash there are plenty of buyers out there for big pharma cast-offs. And these huge developers are no doubt content for this complex and time-consuming activity to be driven externally.

Spin-out success stories 
Company (year of spin out)Parent company Detail 
Viela (2018)AstrazenecaUplizna on the market; $2bn market cap 
Basiliea (2000)Roche Two products to market; $545m market cap
Esperion (2008)PfizerOne product to market; $1bn market cap
Prexton Therapeutics (2012) Merck KGaABought by Lundbeck in 2018 for $125m up front 
Convergence (2010)GlaxosmithklineBought by Biogen in 2015 for $200m up front 
Movetis (2006) Johnson & JohnsonBought by Shire in 2010 for $559m
Actimis (2004)BayerBought by Boehringer Ingelheim in 2008 for $515m
Novexel (2004)SanofiBought by Astrazeneca in 2009 for $505m
Speedel (1998)Novartis Bought by Novartis in 2008 for $880m
Source: EvaluatePharma.

https://www.evaluate.com/vantage/articles/news/corporate-strategy/big-pharma-spinouts-grow

Shanghai Fosun, Sinopharm to supply BioNTech Covid vaccine candidate

Shanghai Fosun Pharmaceutical has signed a strategic cooperation agreement with Sinopharm Group to supply a coronavirus vaccine candidate developed by German firm BioNTech, it said on Monday.

BioNTech announced last month a potential deal with Fosun Pharma to supply 10 million doses of their candidate to Hong Kong and Macau.

The two Chinese firms will work together to set up a cold chain system to store and distribute the vaccine, Fosun Pharma said in a press release.

Separately, a unit of China National Pharmaceutical Group, Sinopharm Group’s parent company, is testing two vaccine candidates in final-stage human trials to combat the virus that has killed over 880,000 people worldwide.

https://www.marketscreener.com/quote/stock/SHANGHAI-FOSUN-PHARMACEUT-6548924/news/Shanghai-Fosun-Pharmaceutical-Pharma-Sinopharm-Group-sign-deal-to-supply-BioNTech-coronavirus-vac-31245595/

Relationship between COVID-19 and obesity

TimurEkizaAhmet CemalPazarlıb

https://doi.org/10.1016/j.dsx.2020.05.047

Dear Editor,

As the high prevalence of obesity in COVID-19 has been shown, the possible interactions between obesity and COVID-19 need to be further deciphered. From this point of view, we determined the obesity prevalence of the top 20 ranked countries by total deaths due to COVID-19. The data regarding the obesity prevalence of countries were obtained from global health services data of the World Health Organization [1,2]. Interestingly, The United States of America ranked first in terms of obesity prevalence (36.2%), overweight prevalence (31.7%), and also the number of total deaths. Overall, most of the countries had a prevalence between 20% and 30% (e.g., UK, Canada, Iran, Mexico, Chile). The obesity prevalence was less than 10% in two countries (India and China) only (Fig. 1). When we look at the correlation analysis between the obesity prevalence and the number of total deaths de to COVID-19, the number of total deaths significantly correlated with the obesity prevalence (p = 0.039, r = 0.464) (Fig. 2). In other words, as the obesity prevalence increased, the number of total deaths increased. It can be said that obesity-related conditions seem to worsen the effect of COVID-19. Herein, we believe that cardiovascular and metabolic effects, sleep apnea, vitamin D deficiency, dysregulation of the renin-angiotensin-aldosterone system (RAAS) as well as sarcopenia should be taken into account as obesity-related confounders to COVID-19. Therefore, highlighting the possible associations of the aforementioned conditions would be reasonable for the fight against COVID-19.

Fig. 1
Fig. 2

The angiotensin-converting enzyme 2 (ACE2) is shown to be the entry point of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This makes sense in patients with obesity because dysregulation/increase of the RAAS has deleterious influences on several systems, has been shown in patients with obesity. For instance, the dysregulation of the RAAS causes vasoconstriction, increased blood pressure, oxidative stress, inflammation, endothelial dysfunction, maladaptive immune modulation as well as fibrosis [3]. As such, obesity is a significant risk factor of diabetes mellitus, increased blood pressure, cardiovascular diseases, and respiratory diseases. Further, myeloid and lymphoid responses within the RAAS receptor signaling are associated with abnormal cytokine profiles. The adipose tissue can manifest as a reservoir for a wider viral spread with increased shedding, immune activation, and cytokine amplification in relevant patients as well [4,5].

On the other hand, obstructive sleep apnea (OSA) is a sleep-related breathing disorder, which is characterized by hypoxia and apnea/hypopnea due to the intermittent collapse of the upper airways during sleep. First of all, obesity is a predominant risk factor for OSA (obesity hypoventilation syndrome), and OSA patients may be vulnerable to COVID-19. Obesity hypoventilation syndrome contributes to respiratory failure in patients with acute respiratory distress syndrome [6]. This fact is vital for patients, particularly with respiratory distress and followed-up in intensive care units [7]. Sleep efficacy has multisystemic effects and is accepted as a very important factor for the regulation and maintenance of the immune system. Worse sleep efficacy is associated with decreased immune system activity [4]. The dysregulation/increase of the RAAS has been shown in OSA patients, likewise in obesity [6].

Vitamin D deficiency, very common in people with obesity, is accepted as another pandemic and has unfavorable impacts on several systems. Immunomodulant, anti-inflammatory and protective effects against infections have been shown. Additionally, it should be kept in mind that vitamin D deficiency worsens obesity by enhancing lipogenesis [8]. On the other hand, sarcopenia, the age-related loss of muscle mass and function, with obesity (sarcopenic obesity) is seen in approximately one-fifth of older populations. Sarcopenia is a physical determinant of frailty, and sarcopenic obesity is highly in association with increased risk of disability, institutionalization, and even mortality [9].

In short, presenting this letter, we would like to highlight that fighting against COVID-19 on the basis of obesity should encompass several multisystem approaches such as inhibition of the RAAS, weight loss, vitamin D supplementation, management of OSA as well as prevention of sarcopenia/frailty.

Funding

None.

CRediT authorship contribution statement

Timur Ekiz: Writing – original draft. Ahmet Cemal Pazarlı: Writing – original draft.

Declaration of competing interest

None.

https://www.sciencedirect.com/science/article/pii/S187140212030165X

Losing ground in COVID-19 vaccine race, CanSino turns to Russia

Politicking between China and Canada threatened to slow down development of a coronavirus vaccine from CanSino Biologics, but the company says the project is back on track following regulatory approval to start trials in Russia.

The Chinese biotech’s adenovirus-based vaccine – developed in alliance with the military – was among the first to start clinical trials as the pandemic gathered pace earlier this year, but development timelines are slipping.

It already has peer-reviewed phase 2 data showing that it can generate antibody and T cell responses against SARS-CoV-2 – the virus that causes COVID-19 – and appears to be safe, although there were some concerns about variability in responses between patients.

The programme has stalled ahead of phase 3 testing however, as other candidates from AstraZeneca/Oxford University, Moderna and Pfizer/BioNTech – as well as Chinese rivals Sinopharma and Sinovac Biotech – have forged ahead.

In May, CanSino formed a pact with the National Research Council of Canada (NRC) to start testing the Ad5-nCoV shot this autumn.

Shipments of clinical trial supplies were held up by Chinese customs in what some claim was an act of retaliation after Canada arrested the chief financial officer of Chinese tech giant Huawei last month at the request of the US government.

Wanzhou has been accused of lying to HSBC in 2013 about Huawei’s business relationship with Skycom, which the US is investigating for violating economic sanctions against Iran.

Towards the end of August the NRC confirmed the end of its partnership with CanSino on Ad5-nCoV, saying: “the process is not clear to the NRC, but CanSino does not have the authority to ship the vaccine at this time.”

Shortly before, Russia granted approval to a multinational phase 3 trial of the vaccine candidate which will be carried out in collaboration with NPO Petrovax Pharm, according to a statement from the Russian company.

“Our teams worked hard for many months to launch the phase 3 clinical trial; this is an excellent example of an international partnership that gains momentum and includes more and more countries,” commented Petrovax Pharma’s president Mikhail Tysferov.

Petrovax Pharma also gains the right to manufacture and distribute the vaccine in Russia following regulatory approval under the terms of the deal, which commentators suggest is part of China’s “COVID-19 diplomacy” – based on forging close ties to countries on good terms with the government in Beijing.

Other countries expected to be involved in the clinical testing of Ad5-nCoV include Brazil, Pakistan, Chile, and Saudi Arabia, with the phase 3 programme expected to recruit around 40,000 subjects, according to a Bloomberg report.

In the meantime, Russia’s home-grown COVID-19 candidate has also generated its first data with its Sputnik V vaccine that according to biotech investor Brad Loncar looks “pretty credible”.

Loncar also tweeted that CanSino “should be kicking themselves for only having tested a one-dose strategy up to this point”, as mid-stage data have looked weaker than other candidates so far.

Medicare Inspector General Plans to Audit COVID-19 Discharges

The OIG will be specifically reviewing claims to determine whether they complied with requirements for the increased MS-DRG weighting. 

The Office of Inspector General (OIG) will be reviewing Medicare payments for the novel coronavirus (COVID-19) discharges, according to a recent update to its Work Plan.

Section 3710 of the CARES Act increased the MS-DRG weighting by 20% for a COVID-19 diagnosis for the duration of the public health emergency.

Effective September 1, COVID-19 claims will require a positive viral test result documented in the medical record to be eligible for the 20% MS-DRG weighting increase.

The OIG will be specifically reviewing claims to determine whether they complied with requirements for the increased MS-DRG weighting.

Organizations should ensure that clinical staff, CDI specialists, coders, and billing staff are aware of the new viral test result requirement.

CDI specialists and coders should query for missing test results. Organizations should consider processes for holding inpatient COVID-19 claims that are pending test results and should review processes for obtaining test results from outside entities.

https://www.healthleadersmedia.com/finance/oig-plans-audit-covid-19-discharges

Healthcare Sector Created 75K New Jobs in August

Most of the jobs came in the ambulatory sector, which had been all but shuttered this spring because of the coronavirus pandemic.


KEY TAKEAWAYS

The August gains included 14,000 jobs in hospitals, 49,000 jobs in physician and dentist offices, and 12,000 jobs in home and health services.

Those gains were offset by the loss of 14,000 jobs in the nursing and residential care sector. 

Healthcare employment is down 679,000 jobs in 2020, including 348,000 job losses in the ambulatory sector, and 104,000 jobs losses in hospitals.

Healthcare sector job growth continued to rebound in August as the nation slowly emerges from the coronavirus pandemic shutdown, but the pace is slowing, according to the latest federal jobs report.

The Bureau of Labor Statistics on Friday reported that the healthcare sector created 75,000 “payroll additions” in August, down from 126,000 new jobs in July, and well below the 318,000 jobs created in June.

The August gains included 14,000 jobs in hospitals, 49,000 jobs in physician and dentist offices, and 12,000 jobs in home and health services. Those gains were offset by the loss of 14,000 jobs in the nursing and residential care sector, BLS said. 

Healthcare employment is down 679,000 jobs in 2020, including 348,000 job losses in the ambulatory sector, and 104,000 jobs losses in hospitals.

August marks the fourth consecutive month of job growth for the healthcare sector, which suffered epic job losses in the spring owing to the coronavirus pandemic. In May, the sector saw 312,000 payroll additions, mostly in outpatient care venues.

The August job report largely reflects the state of the economy in mid-month and is considered preliminary and subject to considerable revision.

In the overall economy, BLS reported that payroll employment grew by 1.4 million in August, down from 1.8 million in July, and the unemployment rate fell to 8.4%.

These improvements in the labor market reflect the continued resumption of economic activity that had been curtailed due to the coronavirus (COVID-19) pandemic and efforts to contain it,” BLS said.

https://www.healthleadersmedia.com/strategy/healthcare-sector-created-75k-new-jobs-august