Starpharma-AstraZeneca combo shows efficacy in leukemia, lymphoma models

Starpharma (ASX: SPL, OTCQX: SPHRY) today announced AstraZeneca’s first patent application on DEPBcl2/xL conjugates has been published by the World Intellectual Property Organisation.

These DEP Bcl2/xL conjugates combine Starpharma’s innovative DEP delivery technology with AstraZeneca’s novel Bcl2/xL inhibitor for treating various cancers, including leukemias.

The published patent application shows compelling efficacy data on DEP Bcl2/xL conjugates, both alone and in combination with other leading current anti-cancer treatments, in various preclinical human tumour models.

As announced on 28 September 2017, AstraZeneca describes its DEP Bcl2/xL conjugate, AZD0466, as ‘best-in-class’ with a broad combination opportunity in both solid and haematological tumours (blood cancers)[1]. Bcl2 is a clinically validated oncology target with the leukemia drug venetoclax (Venclexta – AbbVie/Genentech) approved by the US FDA in 2016. Peak global sales of venetoclax are projected to be greater than US$7 billion[2]. However, venetoclax has only anti-Bcl2 activity and its efficacy may be limited because cancer cells are potentially able to exploit a parallel survival mechanism[3]. Therefore, targeting both Bcl2 and Bcl/xL (as AstraZeneca’s novel DEP Bcl2/xL conjugate AZD0466 does), and using it in combination with other therapies, are attractive strategies that may overcome problematic drug resistance which occurs in many human cancers and thereby provide better efficacy.

Starpharma CEO, Dr Jackie Fairley commented: ‘AstraZeneca’s impressive data published today demonstrates that the DEP Bcl2/xL conjugates are highly effective across a range of cancer types both alone and in combination with other anti-cancer agents. Especially exciting for Starpharma is the combination with blockbuster products such as Rituximab, where the DEP Bcl2/xL conjugates, including AZD0466 showed a strong synergistic effect. Given the synergy appears to also occur with other leading anti-cancer drugs this could represent an important additional benefit for the DEP platform’.

The publication of this patent application results from the highly successful collaborative research effort between Starpharma and AstraZeneca and names inventors from both companies.

Under the AstraZeneca multiproduct DEP licence, Starpharma is eligible to receive potential development, launch and sales milestones of US$124 million for the first DEP product, and US$93.3 million for each subsequent qualifying product. Starpharma will also receive tiered royalties on net sales, and AstraZeneca funds development costs of DEP AstraZeneca products, including these DEP Bcl2/xL conjugates.

Summary of the Published Data

In one study utilising an Acute Lymphoblastic Leukemia model, AstraZeneca compared its Bcl2/xL inhibitor alone to two DEPBcl2/xL conjugates.

Combination therapy is extremely common in cancer treatment to improve efficacy outcomes. The recently published patent also explored the performance of the novel DEP Bcl2/xL conjugates in combination with leading anti-cancer drugs including Rituximab and AstraZeneca’s acalabrutinib (Calquence) in lymphoma models. The efficacy of the DEP Bcl2/xL conjugates in combination with these widely used cancer drugs was extremely impressive, showing significant synergistic effects compared to the drugs alone. This finding is significant, particularly given the fact that this strongly synergistic effect is seen reproducibly.

In a study utilising a B cell Lymphoma model (SuDHL-4), DEP Bcl2/xL conjugates in combination with Rituximab performed much better than Rituximab alone. The combination significantly inhibited tumor growth and resulted in complete tumor regression in most animals, whereas none was seen with single drug treatment.

Rituximab is a leading leukemia therapy sold under the brand names Rituxan and Mabthera. In 2017 Rituximab had sales of approximately US$7.5 billion and is primarily used to treat non-Hodgkin’s lymphoma and chronic lymphocytic leukemia[4].

https://www.marketscreener.com/STARPHARMA-HOLDINGS-LIMIT-8864716/news/Starpharma-AstraZeneca-s-DEP-Bcl2-xL-inhibitors-show-compelling-efficacy-and-synergy-in-combinatio-27200928/

Danone CEO to sit on Carrefour’s healthy food advisory committee

 Carrefour, Europe’s largest retailer, said on Monday that the head of yogurt maker Danone will sit on a food advisory committee the supermarket group is setting up as it seeks to boost sales of organic products.

Carrefour said in January it would revamp its food range and focus more on organic food as customers demand healthier products, under a global five-year plan to increase group sales and profits.

“The group’s ambition is to lead the food transition … This is a big challenge. We absolutely must prove our new positioning to the customer through very strong, precise and coherent actions,” CEO Alexandre Bompard told journalists on Monday.

The new food advisory committee will be led by Carrefour’s Group Secretary General Laurent Vallée, who in January was tasked to spearhead food transformation across the Carrefour group.

It will include seven people from outside the group including a French chef, a farmer, a cancer researcher, as well as Danone CEO Emmanuel Faber, who has said he wants the world’s biggest yogurt maker to play a central role in the revolution sweeping the global food industry.

As more consumers, notably the “Millennial” generation, opt for healthier diets and a more socially responsible way of life, retailers as well as large consumer goods group such as Danone or rival Nestle, have been seeking to adapt.

Danone bought U.S. organic food producer WhiteWave in a $12.5 billion deal, bringing the company more into line with healthier eating trends and its boss will part of a committee that shares best practices and ideas with Carrefour.

Carrefour’s five-year overhaul announced in January also entails cutting costs, boosting E-commerce investment and expansion into convenience stores in the face of fierce competition from more agile rivals like Leclerc, and challenges from online retail giants like Amazon.

Under the plan, Carrefour, which is France’s top organic food retailer, targets 5 billion euros in organic food sales by 2022, compared to 1.2 billion generated in 2017.

“Changing lifestyle habits, an increasing focus on health and food quality as well as growing distrust of the food industry in the wake of recent health scandals is propelling fresh and organic food sales higher in France, allowing retailers to benefit from higher prices and strengthen their earnings and margins, amidst a fiercely competitive environment,” Vincent Gusdorf, senior analyst at Moody’s said in a recent note.

In 2017 organic food sales in France rose 17 percent to 8.4 billion euros from 2016, according to organic food agency Agence Bio.

Carrefour also on Monday unveiled Act For Food, a worldwide program to educate customers about its initiatives to tackle issues such as food safety, product origin and relationships with farmers.

In July, Carrefour bought So.Bio, specialized in the distribution of organic products, with revenue of nearly 40 million euros. So.Bio currently has eight stores in South West France. Carrefour will open three new So.Bio stores by early 2019, including one in Paris and one in Toulouse.

https://www.marketscreener.com/NESTLE-9365334/news/Danone-CEO-to-sit-on-Carrefour-s-healthy-food-advisory-committee-27202566/

France begins vaccinating cows, sheep against anthrax

The eastern French region of Hautes-Alpes said Monday it has begun vaccinating cows and sheep against anthrax after an outbreak of the fatal virus in the region.

Anthrax has been detected in 23 locations, local authorities said in a statement, with 54 animals killed, mainly bovines.

Vaccination doses for 5,000 cows and 10,000 sheep have been rushed to the area to tackle the worst anthrax outbreak in France in nearly 20 years.

Anthrax is an infection spread by spores of the Bacillus anthracis bacteria which occur naturally and can be ingested by livestock and passed on to humans, usually through skin contact, causing black lesions. If left untreated it can be fatal.

 Explore further: Worst anthrax outbreak in 20 years hits French farms

https://phys.org/news/2018-09-france-vaccinating-cows-sheep-anthrax.html#jCp

Brazil court lifts ban on glyphosate weedkiller

An appellate court on Monday lifted a court-ordered suspension of licenses in Brazil for products containing glyphosate, an industrial weedkiller in common use in Latin America’s agricultural powerhouse.

Federal appeals court judge Kassio Marques ruled that “nothing justified” the suspension by a lower court, saying it had been abruptly imposed “without previous analysis of the grave impact it would have on the country’s economy and on production in general.”

The suspension, which had been ordered August 3 by a federal judge in Brasilia, was supposed to go into effect on Monday until a “toxicological re-evaluation” of all products containing glyphosate could be completed by Brazil’s sanitary authority.

The ban also was to have extended to products containing the chemicals thiram and abamectin.

Glyphosate is used in weedkillers like Roundup, made by Monsanto, whose parent company Bayer had urged that the ban be scrapped.

Bayer hailed the suspension as “very good news for Brazilian farmers.”

It comes just weeks after a jury in California ordered Monsanto to pay $289 million to a dying former school groundskeeper for failing to warn him of the risk that Roundup might cause cancer.

That lawsuit built on 2015 findings by the International Agency for Research on Cancer, part of the UN World Health Organization (WHO). It classified glyphosate, Roundup’s main ingredient, as a probable carcinogen, causing the state of California to follow suit.

Studies on the health effects of glyphosate have produced conflicting results, but more than 100 countries authorize its use.

Agricultural products account for nearly half of Brazil’s exports. It is the world’s biggest exporter of soy.

 Explore further: Brazil wrestles with ban of controversial weed killer

https://phys.org/news/2018-09-brazil-court-glyphosate-weedkiller.html#jCp

Liver disease drug could help restore cells damaged by Alzheimer’s

A drug which has been used to treat liver disease for decades could help to restore cells damaged by Alzheimer’s, a new study from the University of Sheffield has found.

The pioneering study, funded by Alzheimer’s Research UK, discovered the drug ursodeoxycholic acid (UDCA) improves mitochondrial dysfunction – which is known to be a causative factor for both sporadic and familial Alzheimer’s disease.

Mitochondria play a pivotal role in both neuronal cell survival and death as they regulate energy metabolism and cell death pathways acting as a cell’s battery.

Mitochondrial abnormalities have been identified in many cell types in Alzheimer’s disease, with deficits occurring before the development of the classical pathological aggregations. The energy changes have been found in many different cells from people with Alzheimer’s. It is thought they are one of the earliest changes to occur in the brain cells, perhaps even before symptoms are reported by people living with the disease.

Dr Heather Mortiboys, Parkinson’s UK Senior Research Fellow at the University of Sheffield’s Institute of Translational Neuroscience (SITraN), said: “For the first time in actual Alzheimer’s patient tissue this study has shown that the drug UDCA acid can boost the performance of the cells’ batteries, the mitochondria.

“We also found that the drug, which is already in clinical use for liver disease, acts by changing the shape of the batteries which could tell us more about how other drugs can be beneficial in Alzheimer’s.

“Most importantly we found the drug to be active in cells from people with the most common type of the devastating disease – sporadic Alzheimer’s – which could mean it has potential for thousands of patients.”
Dr Mortiboys, who led the study, added: “As the drug is already in clinical use for liver disease; this speeds up the potential time it could take to get this drug to the clinic for patients.”

The ground-breaking research also found the drug changed the shape of mitochondria by redistributing Dynamin-related protein 1 (Drp1) to the mitochondria in people with Alzheimer’s skin cells. Drp1 is a regulator of mitochondrial shape and locates at the mitochondria to initiate fission events. It is thought this could have neuroprotective effects in Alzheimer’s disease. This study suggests this pathway could be manipulated by drugs which are then neuroprotective in patients themselves.

The next steps could include studies in patient-derived neurons to check for protective effects or, as others have already shown UDCA to be protective in animal models of Alzheimer’s disease, steps could be taken to move UDCA to clinical trials.

Alzheimer’s disease is the leading cause of dementia worldwide and is the most common neurodegenerative disorder. It currently affects 850,000 people in the UK, with numbers expected to soar to two million by 2051.

Dr Sara Imarisio, Head of Research at Alzheimer’s Research UK, who funded the work, said:”Today, around half a million people in the UK are living with Alzheimer’s disease. With no new dementia drugs in over 15 years, it’s vital we continue to approach Alzheimer’s from as many angles as possible.

“Through innovative research we are building a clearer picture of the complexities of the disease and how it develops in the brain. This work suggests a potential new way to target Alzheimer’s but needs further exploration before we can know whether this drug used for a liver condition is safe or effective for people with Alzheimer’s disease.

“Alzheimer’s Research UK receives no government funding for the research we support, and it is only thanks to the generosity of our supporters that we’re able to fund vital projects like this.”

Previous laboratory studies conducted by SITraN in 2015 showed UDCA could be an effective treatment in halting the progression of Parkinson’s disease. The collaborative study demonstrated the effects of the drug in patients that carry the LRRK2 mutation. The study showed improved mitochondrial function as demonstrated by the increase in oxygen consumption and cellular energy levels.

The new research is published in the Journal of Molecular Biology.

 Explore further: Vitamin C deficiency and mitochondrial dysfunction in Alzheimer’s disease

https://medicalxpress.com/news/2018-08-liver-disease-drug-cells-alzheimer.html

With Consolidation Wave, Cannabis Industry Rises To Next Level

Large corporations are still squeamish about investing in cannabis. This means great opportunities for smaller players

At the end of July, the cannabis industry watched as two Canadian companies set a new record. Aurora Cannabis acquired MedReleaf (another Canadian cannabis producer) for CA$3.2 billion — $2.3 billion in U.S. dollars. This, the largest cannabis acquisition to date, created a company capable of producing 570,000 kilograms of high-quality cannabis per year at a cost of below $1 per kilogram.

It was a validating moment for those of us in the industry. Cannabis as a business is still in its infancy. For the most part, we’re a group of entrepreneurs who were willing to take a chance on a product that, until recently, might have landed us in jail (or, at least, in some trouble with state authorities). The increase in mergers and acquisitions shows that we were smart to take the risk. In the first half of 2018, M&A activity nearly doubledfrom a year earlier to 145 deals in North America, according to Viridian Capital Advisors. Through June 22, public and private cannabis companies have raised $4 billion, up from $1.3 billion just one year ago.

Right now, the biggest deals are happening in Canada, which the U.S. market looks to as our future. While cannabis is still considered a Schedule 1 narcotic at the federal level here (despite the fact that it is legal to use and buy in two-thirds of the nation), the herb was recently legalized in Canada. That has not only paved the way for Canadian citizens to reap the medical and recreational benefits of cannabis, it also means Canadian companies can tap the financial markets, something U.S. companies still struggle to do.

It’s worth noting that Aurora initiated its purchase of MedReleaf in May, a month before the Canadian Senate voted to legalize cannabis. At that point, big public companies were still pretty much shut out of the market. They didn’t want to risk acquiring businesses that might not become nationally legal and even if they wanted to, it’s unlikely banks would have been willing to underwrite or finance such purchases.

Aurora was able to buy MedReleaf in an all-stock deal. In the post-legal Canadian world, the market is now open to all comers as Canadian banks will have no problem working with corporations to finance mergers and acquisitions.

While that means many small companies are now attractive acquisition targets, it also means that big alcohol and pharmaceutical companies will be sniffing around Canadian cannabis companies. Constellation Brands, the company behind beers such as Corona and Modelo, has already made a significant investment in Canopy Growth, an Ontario-based cannabis producer. Last October, Constellation bought a 9.9% stake in the Canadian company. In June, Constellation bought another third of the company. Then in August, the alcohol company bought another 104.5 million shares in a deal worth CA$4.5 billion ($3.45 billion in U.S. dollars). If Constellation ends up buying Canopy, as many on Wall Street are speculating, it will dwarf that Aurora MedReleaf acquisition.

Back in the states, the numbers are smaller but the market is no less busy. MedMen, the fast-growing cannabis retailer, has made a slew of acquisitions including its recent purchase of Treadwell Nursery, a cannabis grower and distributor in Florida, for $53 million. In May, four cannabis companies joined forces to create TILT Holdings, which builds cultivation facilities, sells software to help manage the process and offers financing to the cannabis industry. The combined company expects to bring in $70 million this year. And at my company, KushCo Holdings, we’ve made four recent acquisitions that enhance our creative branding capabilities and help us expand into vaporizers and the gas and solvents needed to extract oils from cannabis to produce concentrates.

At some point, the U.S. market is going to get big enough for companies such as Constellation to justify making cannabis acquisitions here, especially if the government eases restrictions on national banks so they can work with cannabis companies without risking legal repercussions. The window before that happens is small. Before it closes, expect to see more M&A activity among established U.S. companies in the hopes that they will become big enough to fend off the larger competition when it inevitably comes calling.

Nick Kovacevich is the CEO and cofounder of KushCo Holdings, Inc. (OTCQB: KSHB) the parent company to a diverse group of business units that are transformative leaders in the cannabis, CBD and other related industries. 

https://www.forbes.com/sites/nickkovacevich/2018/08/29/with-a-wave-of-consolidation-the-cannabis-industry-rises-to-the-next-level/#43f9eb4ef368

EMA freezes UK representatives out of drug reviews as Brexit looms

The UK’s drugs regulator is increasingly being frozen out of work with the European Medicines Agency (EMA) according to a press report, dealing a blow to the government’s hopes that it could play a leading role in European drug reviews after Brexit.

With Brexit talks progressing at a snail’s pace and the deadline of March 29th looming, the EMA has been preparing for a “no-deal” situation where the UK becomes a third country and plays no part in the European drugs regulation system.

And the latest report casts doubts about the prime minister’s plans for the UK to continue with its involvement with the EMA after Brexit.

The Guardian reported that the EMA has ceased to appoint experts from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) to oversee centralised reviews of more complex medicines.

These so-called rapporteurs, who can be appointed from any EU country, follow the progress of a medicine as it goes through the EMA’s committee process.

And until the Brexit vote in 2016 the UK played a leading role in this process, providing more rapporteurs than any other country.

But the EMA said that as the Brexit deadline approaches, and with the MHRA looking set to cut its ties with Europe along with the UK and the rest of its agencies, it cannot be confident that MHRA staff will be able to follow the entire review process for recently filed drugs.

EMA reviews usually take around a year, meaning that any drugs that are filed now will still be in the middle of their review when Brexit happens in March.

Rapporteur work being carried out by the MHRA is also being reallocated to representatives from other EU countries.

Martin McKee, professor of European public health at the London School of Hygiene and Tropical Medicine, told the Guardian that the changes are a “disaster” for the UK’s MHRA, which earns around £14 million from the EMA.

In 2016 the EMA appointed 22 rapporteurs to review new medicines, but in 2017 it appointed just six.

Mike Thompson, chief executive of the Association of the British Pharmaceutical Industry (ABPI), said the process is like the end of a “British success story”.

Pharma companies are already having to build extra labs to batch release medicines made in the UK on the continent.

Thompson added that this is “hundreds of millions of pounds” that could be spent on researching new medicines, but the industry has “no choice” as it has to comply with regulations.

The EMA is in the process of moving around 900 staff from its London offices, to Amsterdam, which will be its new home after Brexit.

The MHRA said in a statement: “We want to retain a close working partnership with the EU to ensure patients continue to have timely access to safe medicines and medical devices. This involves us making sure our regulators continue to work together, as they do with regulators internationally and we would like to explore with the EU the terms on which the UK could continue to participate in the EMA.”

Some elements of the MHRA’s role will change during the Implementation Period. For example, for medicines – as with all areas – the UK will no longer have voting rights in the EMA and EU committees, and MHRA will no longer lead assessments on behalf of the EMA to inform their decision-making process.

“We are currently considering the potential impact of different Brexit outcomes on MHRA. It is important to remember the bulk of agency regulatory work is national, as is its income, said the MHRA.”

A spokesperson for the ABPI said: “The strength of the MHRA has been key to the overall strength of the European regulatory system.”

“The ABPI has been clear that we want to see as close cooperation as possible between the MHRA and the EMA.  As we enter the final stages of the Brexit negotiations, we are looking for politicians to make this central to the future UK-EU relationship.”

“Continued cooperation in the long standing systems to protect patient health, control infectious diseases and manage medicine safety is in the best interests of patients in the UK and the EU.”

https://pharmaphorum.com/news/ema-freezes-uk-representatives-out-of-drug-reviews-as-brexit-looms