Category Archives: Immunology

Sequiris invest £40m into expansion of Liverpool plant creating 100 new jobs

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The Liverpool-based vaccine-maker Sequiris is investing £40 million into the expansion of its operations in the Speke area of Liverpool.

The multi-million pound investment is set to create 100 new jobs while allowing vaccines to be created more quickly in preparation for outbreaks of the flu. While vaccines are currently shipped to Italy for packaging, the expansion will now allow the process of packing the vaccines into syringes and capsules to be done in the UK.

The company, which is as of now the second biggest influenza vaccine company in the world, provides around half of the vaccines used in the UK. The project which is expected to be complete in 2019 will increase the safety of the government contracted vaccine makers products.

The investment will also increase the speed with which vaccines reach the market in the UK.

Dr Laura O’Brien, vice president of operations and site head at Liverpool, commented: “This investment means we can complete production of more pandemic vaccine much more rapidly, saving vital days in getting vaccines out to protect the British population as well as to other countries around the world.”

SOURCE: www.pharmafile.com/news/519043

Bacterial therapy shows early promise in patients with advanced solid tumours

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Researchers have presented results of a Phase I clinical trial using bacterial Clostridium novyi-NT spores to target advanced solid tumours.

A Phase I clinical trial that investigated the use of bacterial Clostridium novyi-NT spores as an injectable monotherapy showed toxicities that were manageable and early clinical efficacy in patients with treatment-refractory solid tumour malignancies.

“Even after a single injection of this bacterial therapy, we see biological and, in some patients, clinically meaningful activity,” said Dr Filip Janku, Associate Professor at the Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Centre, Houston.

“This strategy is feasible, has manageable adverse effects, and could be clinically meaningful in patients with few therapeutic options.”

Previous therapies have tested the use of bacteria, but have often caused infection. In this study, the use of C. novyi-NT spores in the open-label, first-in-human study, the researchers explained how a hypoxic environemnt is necessary for the bacterium. It requires a feature of cancerous lesions to survive and proliferate, and thus does not affect healthy cells.

“By exploiting the inherent differences between healthy and cancerous tissue, C. novyi-NT represents a very precise anticancer therapeutic that can specifically attack a patient’s cancer,” Prof Janku said.

Between 2013 and 2017, 24 patients were enrolled with treatment-refractory solid tumors, with 15 patients having sarcoma, seven patients having diverse carcinoma and two with melanoma.

Tumours were injected with a single dose of C. novyi-NT, from 10,000 to 3 million spores. Patients administered with 3 million spores experienced dose-limiting toxicities of grade 4 sepsis, and as such the highest tolerated dose was determined to be 1 million spores.

Tumour shrinkage of greater than 10 percent was identified in 23 percent of the patients, and 21 had stable disease, measured by RECIST. Prof Janku mentioned that RECIST may not accurately capture results of the trial.

“Despite the absence of clinical signs of germination in some patients, we saw improved tumor-specific immune responses through the increased secretion of T-cell cytokines and increased presence of tumor infiltrating lymphocytes in injected tumors,” said Prof Janku.

“From these preliminary results, it appears that C. novyi-NT is able to activate the immune response besides causing tumor destruction.”

C. novyi-NT elicits an immune response, and as such Prof Janku believes this therapy will be synergistic with checkpoint inhibition.

“We were extremely encouraged by the results of this trial, especially in patients with advanced sarcomas, where immunotherapy hasn’t proven very efficacious,” Prof Janku concluded. “This bacteriolytic strategy has the potential to be clinically meaningful, especially in combination with checkpoint inhibitors, for patients with advanced solid tumors.”

The data was presented at the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival.

SOURCE: www.europeanpharmaceuticalreview.com/news/79682

Ipsen appoints two leading R&D experts in bid to strengthen oncology arm

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French pharma firm Ipsen has announced the appointment of Dr. Yan Moore as Senior Vice President, Head of Oncology Therapeutic Area and Dr. Alexander “Sandy” McEwan, as Vice President, Head of Radiopharmaceuticals.

It is hoped that the move, which has seen the company take on two leading oncology specialists within a month of each other, will strengthen the company’s oncology arm.

Alexandre Lebeaut, Executive Vice President R&D and Chief Scientific Officer, Ipsen, commented: “I am thrilled to welcome Yan and Sandy as talented leaders who will assume pivotal roles in the next phase of our R&D transformation, and whose unique goal is to accelerate the development and deliver innovative therapeutic solutions to cancer patients.”

While Tel Aviv University graduate Dr Moore’s appointment with the Paris-headquartered company is effective immediately, Dr McEwan will join Ipsen on November 1st. Both R&D leaders will report to Dr. Alexandre Lebeaut, Executive Vice-President R&D and Chief Scientific Officer.

Dr Moore brings with him a wealth of experience from large multinationals including Bristol-Myers Squibb. Sanofi-Aventis and GlaxoSmithKline. Commenting Lebeaut said: “Yan is an outstanding biopharmaceutical executive who brings over 18 years of industry experience in oncology development across solid tumors, hematology‐oncology, gene and immune‐therapy. In his new role, Yan will lead and further strengthen our global oncology development powerhouse.”

Meanwhile McEwan, the author of more than 900 articles in peer reviewed journals and past President of the Society of Nuclear Medicine and Molecular Imaging, joins the organisation from the University of Alberta in which he held positions as Professor in the Department of Oncology and Adjunct Professor for the Department of Radiology and Diagnostic Imaging.

Lebeaut noted: “Sandy is a world-renowned expert in oncology and nuclear medicine who brings to Ipsen unique experience in this field. He will play a defining role in the acceleration of the development of Ipsen’s radiotherapeutics pipeline, providing strategic direction and managing the execution of the global clinical development of both satoreotide tetraxetan (IPN01072) and Satoreotide Trizoxetan (IPN01070) and also IPN01087 programs. Sandy will build and maintain trustworthy relationships with external oncology and nuclear medicine experts, academic networks, and professional organizations.”

SOURCE: www.pharmafile.com/appointment/518915

Cancer immunotherapy pioneers awarded Nobel medicine prize

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Cancer immunotherapy pioneers James Allison and Tasuku Honjo have been awarded this year’s Nobel Prize in Physiology or Medicine.

The Karolinska Institutet’s Nobel Assembly awarded the prize for their discovery of cancer therapy “by inhibition of negative immune regulation.”

The work by Allison and Honjo paved the way for drugs such as Bristol-Myers Squibb’s Yervoy (ipilimumab), which work by turning off the safety mechanisms in the immune system that prevents it from attacking the patient’s own body.

This allows the immune system to launch an attack against cancer – a mechanism that is fast becoming the basis for standard therapy in diseases such as melanoma and lung cancer.

Allison, currently professor and chair of Immunology and executive director, immunotherapy platform at the M. D. Anderson Cancer Center, studied a known protein, cytotoxic T-lymphocyte associated protein-4 (CTLA-4), that functions as a brake on the immune system.

He realised the potential of releasing the brake and thereby unleashing our immune cells to attack tumours. He then developed this concept into a brand new approach for treating patients.

Inhibition of CTLA-4 is the mechanism exploited by Bristol-Myers Squibb’s Yervoy (ipilimumab), the first checkpoint inhibitor approved by the FDA in 2011, to treat melanoma.

Honjo, now deputy director-general at the Kyoto University Institute for Advanced Study (KUIAS), discovered the programmed cell death protein (PD-1)  protein on immune cells.

After careful exploration of its function, he eventually revealed that it also operates as a brake, but with a different mechanism of action.

In inhibition of PD-1, or its ligand, PD-L1, it forms the basis for all the other checkpoint inhibitors approved so far, including Merck’s blockbuster Keytruda (pembrolizumab).

In its statement the Nobel assembly noted that although PD-1 had proved to be more effective overall, combining the two forms of therapy could be even more effective, as demonstrated in patients with melanoma.

(c) Nobel Media

James Allison

The committee concluded in its statement: “Allison and Honjo have inspired efforts to combine different strategies to release the brakes on the immune system with the aim of eliminating tumour cells even more efficiently.

(c) Nobel Media

Tasuku Honjo

“A large number of checkpoint therapy trials are currently underway against most types of cancer, and new checkpoint proteins are being tested as targets. For more than 100 years scientists attempted to engage the immune system in the fight against cancer. Until the seminal discoveries by the two laureates, progress into clinical development was modest. Checkpoint therapy has now revolutionised cancer treatment and has fundamentally changed the way we view how cancer can be managed.”

In a statement, Shigefumi More, director general and distinguished professor at KUIAS, said: “It is wonderful that the efficacy of cancer immunotherapy by PD-1 blockade has now been demonstrated worldwide, and that this therapy is actually saving the lives of many people. I would like to express my respect for his important work for human beings, and wish Distinguished Professor Honjo continued success in the future.”

SOURCE: www.pharmaphorum.com/news

Roche buys Tusk, plus cancer immunotherapy drug, for £62m

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Roche has bought immuno-oncology biotech firm Tusk Therapeutics for an upfront payment of £62 million.

Tusk’s shareholders will receive the upfront cash payment, plus additional contingent payments of up to £521 million, if and when certain milestones are achieved.

Tusk, which is based in Stevenage, has developed a first-in-class antibody, CD25, for the depletion of regulatory T-cells (TRegs), which suppress the body’s immune reaction to cancer cells.

This novel antibody enables the body’s other immune cells to fight tumours while leaving healthy tissue unharmed. Clinical trials are expected to start next year.

Luc Dochez, CEO of Tusk Therapeutics, said: “We are delighted that Roche will further develop this novel antibody and drive the development ahead.

“The remaining portfolio of our immune-oncology targets will be further developed by Black Belt Therapeutics, a newly formed company spun out of Tusk Therapeutics.”

Droia Oncology Ventures, Tusk’s majority shareholder, founded the company in 2014. Droia is a specialist investor, which focuses on fighting cancer.

It invests in promising new cancer therapies and accelerates their progress by actively supporting young drug development companies to achieve clinical proof of concept with their lead programmes. The deal will expand Roche’s oncology pipeline.

Also, Roche today announced a new collaboration with Novo Nordisk, which specialises in the treatment and management of diabetes and obesity.

The plan is to integrate insulin dosage information from Novo Nordisk’s connected pen technology into Roche’s open ecosystem, whereby it will communicate with its digital diabetes management solutions including mySugr, which allows people to monitor their glucose levels.

Marcel Gmuender, global head of Roche Diabetes Care, said: “The integration of insulin pen data in our digital health solutions such as mySugr will make it much easier for people with diabetes and their caregivers to track the effect of insulin on blood glucose levels.

“This enables more efficient and targeted decision support, as they can act on near real-time insights to optimise the personalised diabetes management, thereby reducing the risk of costly secondary complications and contributing to improved therapy outcomes and better quality of life.”

Anders Toft, corporate vice president of commercial innovation at Novo Nordisk, echoed this, adding: “Digital health solutions like mySugr are already helping thousands of patients. By integrating Novo Nordisk connected technology with mySugr, we can further ease the day-to-day burden of disease management and provide data-based insights to improve the dialogue between patients and caregivers.”

SOURCE: www.pharmaphorum.com/news

Paracetamol use in infancy may increase the risk of asthma

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A study has found that paracetamol use in infancy, as well as genetic factors, may increase the likelihood of developing asthma.

A study by researchers from the University of Melbourne, Australia identified how infants who take paracetamol during the first two years of life could be at a higher risk of developing asthma in their late teens.

Xin Dai, a PhD candidate at the University, and her colleagues explained how the link between paracetamol use and asthma seemed to be the strongest in individuals with a particular variant of the glutathione S-transferase (GST) gene, GSTP1.

GSTP1 is part of a gene family which encodes gene crucial for some life processes, detoxification and toxification mechanisms. The genes are upregulated in response to oxidative stress, and are overexpressed in tumours.

GST genes contain the information needed to make the antioxidant glutathione, which clears the effect of exposure to toxins in the body and the lungs.These actions help to prevent damage to cells and inflammation.

“Paracetamol, on the other hand, consumes glutathione, reducing the body’s capacity to deal with toxic exposure,” said Ms Dai. “We hypothesised that people who did not have full GST enzyme activity because of common genetic variations or deletions may be more susceptible to adverse effects on the lungs from paracetamol use.”

The researchers investigated 620 children who had been followed form birth to the age of 18, as part of the Melbourne Atopy Cohort Study. These children were selected before birth, as it was deemed that they had a high risk of developing an allergy-related disease. At least one family member (father, mother or sibling) had a self-reported allergic disease, such as asthma, eczema, hay fever or a severe food allergy.

After the birth of each child, a nurse rang the family every four weeks for the first 15 months, and then at 18 months and at two years old to ascertain the number of time the infant was given paracetamol. As the child reached the age of 18, a blood or saliva sample was given and tests were conducted to identify variants of GST genes.

The participants were also assessed for asthma, and a spirometry test measured the amount of air inhaled and exhaled when breathing through a mouthpiece.

“We found that children with the GSTP1 Ile/Ile variant had 1.8 times higher risk of developing asthma by the age of 18 years for each doubling of the days of paracetamol exposure when compared to children who were less exposed,” said Ms Dai. “In contrast, increasing paracetamol exposure in children who had other types of GSTP1 did not alter the risk of asthma.

In addition, we found some weak evidence that paracetamol use in the first two years of life may be associated with reduced lung function in adolescence regardless of which variants of the GST genes the children had.”

The researchers stressed that the study showed an association between paracetamol and asthma, and not that one caused the other. To establish this, further research would be necessary.

She concluded: “Our findings provide more evidence that paracetamol use in infancy may have an adverse effect on respiratory health for children with particular genetic profiles and could be a possible cause of asthma. However, these findings would need to be confirmed by other studies and the degree of adverse effect better understood before this evidence could be used to influence practice and before guidelines on paracetamol use are altered.

“There is mounting evidence that the GST superfamily of genes, including three major classes -GSTM1, GSTT1 and GSTP1 – are associated with various diseases, including cancers, asthma, atherosclerosis, allergies, Alzheimer’s and Parkinson’s disease. Our study adds to this body of evidence.”

The study was presented at the European Respiratory Society International Congress.

SOURCE: www.europeanpharmaceuticalreview.com/news/79189

New C.diff drug to be tested on patients for first time

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A new drug aimed at treating potentially deadly Clostridium difficile (C. diff) infections is set to be tested on patients for the first time.

Glasgow-based life sciences firm MGB Biopharma (MGB) said it was preparing to launch a Phase II clinical trial of its anti-bacterial agent MGB-BP-3.

The trial is expected to involve 30 patients based in North America.

All have been diagnosed with C.diff-associated disease (CDAD).

C.diff infections can cause diarrhoea and fever.

They have been a major problem in hospitals around the world, with thousands of deaths in the US alone linked to the bug each year.

The bacteria are able to take over the gut when a course of antibiotics kills off the bugs that normally live there.

MGB’s announcement came after it raised £1.3m from investors for trials of the new drug, which was invented at the University of Strathclyde.

The funding round was led by Edinburgh-based Archangels, with co-funding from a range of sources, including the Scottish Investment Bank, Barwell and Melrose-based Tri Capital.

The cash supplements a £2.7m grant awarded earlier this year by Innovate UK.

MGB said its trial would “evaluate safety and tolerability, efficacy and in particular look for improvement in global (or sustained) cure rates”.

Chief executive Dr Miroslav Ravic said: “We are already witnessing renewed interest in our new anti-bacterial agent and its trial in key medical centres in North America where CDAD is particularly prevalent.

“This offers opportunities both to progress the study rapidly and to attract increased attention to the results for this important trial.”

The company said it was aiming to start the trials in areas of the US and Canada with a high incidence of CDAD early next year.

SOURCE: www.bbc.co.uk/news/

Celgene’s Otezla produces “meaningful benefits” beyond beyond traditional metrics in plaque psoriasis

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Celgene made its voice heard amongst the chorus of new psoriasis data emerging from the European Academy of Dermatology and Venereology (EADV) Congress in Paris, revealing that Otezla (apremilast) achieved “meaningful improvements” in outcomes of patients with moderate to severe plaque psoriasis that may not be captured by common metrics that focus only on skin clearance, such as the Psoriasis Area Severity Index (PASI).

“Only considering skin clearance may not fully capture the effect a treatment may have on an individual’s disease burden and its impact on daily life,” explained Dr Denis Jullien, Department of Dermatology and Venereology at Edouard Herriot Hospital, and an author of the study. “For example, itching, which is not accounted for by PASI, is cited by over a third of patients as their overriding quality-of-life issue. These new analyses of Otezla studies can help inform both prescribers and patients when evaluating treatment decisions.”

The new findings included a post hoc sub-analysis of the phase 3 ESTEEM 1 trial, examining moderate to severe plaque psoriasis patients who did not achieve a PASI score of 75 after either 32 or 52 weeks of treatment with Otezla during the trial. In this group, over half achieved a 50% reduction in PASI score over the same periods – findings that Celgene argues “may more reliably indicate clinically meaningful benefit” when taken together with disease-specific quality-of-life measures.

For example, the data showed that itching was reduced from baseline by around 30% during weeks 4 to 52 for those who started treatment of Otezla, and during weeks 20 to 52 in patients who were switched form placebo at week 16. Additionally, patients reported an increase of at least five points in the Dermatology Life Quality Index (DLQI) over the same period.

“The ESTEEM and UNVEIL clinical trials continue to provide important learnings about Otezla for the treatment of psoriasis as well as quality of life for people who live with this chronic condition,” said Volker Koscielny, Vice President of Global Medical Affairs, Inflammation & Immunology at Celgene. “These sub-analyses of UNVEIL and ESTEEM suggest that appropriate patients with moderate to severe plaque psoriasis who experience manifestations beyond skin may benefit from treatment with Otezla.”

SOURCE: www.pharmafile.com/news/518748

Boehringer Ingelheim joins the crowd and goes all-in on oncolytic viruses, buying ViraTherapeutics in $244M deal

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Boehringer Ingelheim decided 3 years ago it that would take an active role in fostering the oncolytics virus biotech ViraTherapeutics.

The German company’s venture arm invested in the fledgling’s biotech’s tiny $4 million A round in the summer of 2015. BI execs came back with a $230 million discovery deal — building in a buyout option — and then added a second program. And this morning they’re going all in, buying the company in a deal valued at $244 million.

BI is keeping the company — a spinout of Austria’s Medical University of Innsbruck — right where it is, adding the group and the regional connections they have on campus as a subsidiary as they look to jump into the clinic with a lead program.

Boehringer first tied up with ViraTherapeutics just months ahead of Amgen’s landmark approval of T-Vec, the world’s first marketed oncolytic virus. And since then the field has exploded with new research projects as dozens of new players brewed up to beat the pioneer.

Earlier this year J&J executed one of its classic billion-dollar deals to buy BeneVir. Merck’s R&D chief Roger Perlmutter — who steered the T-Vec deal at Amgen — bagged Viralytics for $394 million. A recent study from the Cancer Research Institute found 69 OVs in clinical development and another 95 in a preclinical program.

What’s the big deal?

Oncolytic viruses are the Trojan horse of immuno-oncology. The viruses are designed to infect cancer cells, invading the disease, and then exploding them, which subsequently signals the immune system to mount an attack on the survivors. There’s a clear clinical track record showing how they work. And now a host of rivals like PsiOxus and many, many others believe that systemic administration will do a better job.

ViraTherapeutics execs — led by MorphoSys vet Heinz Schwer — have also been busy engineering an OV therapy that they believe can do a better job of initially evading detection by the immune system, avoiding triggering any antibodies and theoretically making it possible to do repeat administrations.

Not surprisingly, BI also plans to whip up a pipeline of combination approaches, arming their OV with cancer drugs that can both amp up the immune system attack and charge directly at cancer cells.

SOURCE: www.endpts.com

Gilead, Galapagos JAK inhibitor clears phase II test

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A mid-stage trial of Gilead and Galapagos’ JAK1 inhibitor filgotinib has set up a phase III programme for the drug in ankylosing spondylitis as it chases down two already-marketed dugs from Pfizer and Eli Lilly – and a late-stage rival from AbbVie.

In the TORTUGA trial, filgotinib met its clinical objective of reducing disease activity scores compared to placebo in patients with AS, a severe form of arthritis affecting the spine, with more patients achieving the target 20% improvement with the drug (76%) than in the control group (40%).

The drug is also in development for rheumatoid arthritis (RA), ulcerative colitis and Crohn’s disease with phase III trials already underway in those indications and results due in the coming weeks.

The drug was generally well-tolerated in TORTUGA but one case of deep vein thrombosis gave investors some cause for concern, putting some pressure on Gilead and Galapagos’ share price yesterday before share staged a partial recovery.

DVT is a recognised side effect with Eli Lilly’s JAK1 inhibitor Olumiant(baricitinib), which finally made it to market for rheumatoid arthritis in Europe last year but was rejected in the US at its first filing attempt over the safety issue. Gilead said that in the phase II AS trial the patient had an inherited condition that raised the risk of blood clots and the DVT was not thought to be drug-related.

First-to-market JAK inhibitor Xeljanz (tofacitinib) from Pfizer has already achieved $1bn-plus sales in RA, and with Olumiant somewhat hamstring by the safety issue on its label analysts are viewing the tussle between filgotinib and AbbVie’s upadacitinib as the next big battleground in the JAK inhibitor market.

AbbVie is a little ahead in the race to market, with phase III data in hand showing that upadacitinib is more effective than AbbVie’s $18bn-a-year injectable TNF blocker Humira (adalimumab) in RA when it comes to clinical responses gauged by doctors and patients. Like filgotinib, upadacitinib is also being tested in a string of other indications, including psoriatic arthritis, Crohn’s disease, ulcerative colitis and atopic dermatitis.

The rivalry is particularly strong as AbbVie was formerly Gilead’s partner for filgotinib, before ducking out of the collaboration and throwing its weight behind its in-house candidate.

SOURCE: http://www.pmlive.com/pharma_news