30.11.2012 - Selecta Biosciences and Sanofi have signed a global collaboration to develop antigen-specific immunotherapies for up to three allergy indications.
The US-based biotech has developed a synthetic vaccine particle technology which is now being licensed to the French pharma for up to US$900m including a number of milestone payments. The agreement gives Sanofi the right to develop a therapy to fight an immune response triggered by a life-threatening food allergen. Furthermore, Sanofi may develop two other compounds. The pharma got in touch following the lure of the technology discovered in the lab of Bob Langer at the MIT.
Selecta engineers nanoparticles with the structure required to stimulate immune tolerance thereby controlling overactive response to antigens. Selecta won substantial backing from RusNano last autumn, agreeing to set up operations in Russia as part of the deal. Privately held Selecta is a shooting star since its foundation in 2008, raising more than US-$32m in three venture rounds, finally attracting the attention of Rusnano. Last year, the US$10bn Russian fund joined Selecta’s existing investor base. The consortium spent US$47.25m to broaden the company’s R&D capabilities and accelerate its pipeline of vaccines and immunotherapies.
26.01.2014 Dutch Contract Manufacturing Organisation Pharmacell B.V. will purchase
Tigenix N.V.'s cell therapy production facility near Maastricht.
Under the agreement, Dutch Pharmacell is set to purchase shares of Tigenix B.V., which holds the manufacturing site. The deal is subject to certain closing conditions and the companies intend to complete the transaction in the coming months. Pharmacell will acquire the facility, including its employees in production, QC, QA and other functions.
The Tigenix cartilage repair product Chondrocelect will continue to be manufactured at the facility as before, under a long-term CMO agreement with Pharmacell. In 2012, Tigenix's state-of-the-art manufacturing facility passed cGMP inspection by the Dutch authorities and obtained approval from the European Medicines Agency for the production of Chondrocelect, the company's commercial cell therapy product for cartilage repair in the knee. Going forward, Pharmacell intends to produce other commercial and investigational cell therapy and regenerative medicine products at the site.
Alexander Vos, CEO of Pharmacell B.V. said: "The new partnership with Tigenix is a further step forward to strengthen our business in support of the development of the cell therapy industry in Europe. Pharmacell and Tigenix have created a collaborative business model for cell therapeutics in general and for Chondrocelect in particular."
24.01.2014 Prothena Corp has received an initial payment of €22m from Roche as part of its €443m Parkinson's deal.
The antibody spin-off from Irish Elan Corp, which was taken over last summer by Perrigio, will receive a further €11m upfront when its anti-synuclein antibody RPRX002 enters clinical trials this summer and up to €410m in milestones and royalties, under the agreement announced in December 2013.
Prothena's monoclonal antibody for the treatment of patients with Parkinson's disease is currently in preclinical development and is expected to enter Phase 1 clinical trials in H1/2014. It targets α-synuclein, a protein that is found extensively in neurons and is a major component of the pathological inclusions that characterise several neurodegenerative disorders such as Parkinson’s disease, dementia with Lewy bodies, neurodegeneration with brain iron accumulation type 1 and multiple system atrophy.
PRX002 has been tested in various cellular and animal models of synuclein-related disease. Passive immunisation with 9E4, the murine version of PRX002, in multiple transgenic mouse models of Parkinson's disease, reduced the appearance of synuclein pathology, protected synaptic connections and improved performance by the mice in behavioural testing. Roche’s Pharma Research and Early Development (pRED) in Basel most recently reported a new technology able to transfer antibodies across the blood brain barrier boosting its therapeutic effect by a factor of 55. Within the collaboration with Prothena, Roche will make use of this so-called brain shuttle technology.
23.01.2014 Audi takes the next step for its plans to promote non-fossil fuels. The carmaker has launched a 2-year strategic partnership with French biotech Global Bioenergies.
Global Bioenergies and Audi will collaborate in the development of isobutene-derived isooctane, a high performance biofuel for gasoline engines. The new fuel, called e-gasoline, is part of the overall Audi e-fuels strategy. With e-gas and e-diesel, the car manufacturer is already running several projects on alternative fuels. Reiner Mangold, Head of Sustainable Product Development at Audi AG commented: “We are supporting an innovative technology here, which can be used to produce renewable fuel. This process does not create competition with food production and farmland.”
Evry-based Global Bioenergies specialises in the development of processes for the transformation of renewable resources into light olefins, the key building blocks of the petrochemical industry. Among others products, the company produces bio-isobutene, a molecule with multiple applications, one of which allows its transformation into isooctane, the gold standard for gasoline engines (octane number 100). As a 100% drop-in fuel, it can be used in any blending ratio with all standard fuels for gasoline motors. Thomas Buhl, Head of Business Development at Global Bioenergies said: “We had recently announced the start of our pre-commercial pilot phase at the Fraunhofer CBP in Leuna, allowing us to obtain high-purity isobutene which can be used for different applications. One crucial point of our collaboration with Audi will consist of supplying them with isooctane derived from our isobutene, to be produced at that pilot.”
22.01.2014 Danish researchers have identified diagnostic microRNA panels in whole blood that can discriminate patients with and without pancreatic cancer.
Although the findings reported in the current issue of JAMA (doi:10.1001/jama.2013.284664) are preliminary, a test would have the potential to detect one of the most deadly cancers earlier in its development. Nicolai A. Schultz from Copenhagen University and colleagues examined differences in microRNA in whole blood taken from 409 patients with pancreatic cancer and 312 healthy participants as well as 25 patients with chronic pancreatitis to identify diagnostic panels of microRNAs for use in the diagnosis of pancreatic cancer. Serum cancer antigen 19-9 (CA19-9) – an antigen that is elevated in approximately 80% of patients with pancreatic cancer – was also measured for comparison.
The researchers identified two novel panels with the potential for diagnosing pancreatic cancer. The authors write that the test could result in referral of more individuals with symptoms to imaging. "The test could thereby diagnose more patients with pancreatic cancer, some of them at an early stage, and thus have a potential to increase the number of patients that can be operated on and possibly cured of pancreatic cancer." They add that the harms of a high number of false-positives in screening for pancreatic cancer using an inexpensive, non-invasive blood sample from individuals with or without symptoms should be quantified in the future.
Pancreatic cancer is the fourth most common cause of cancer death in the Western world and prognosis is poor. Early diagnosis of pancreatic cancer is difficult, in part because it is difficult to get useful biopsies of tissue from patients suspected of having pancreatic cancer, thus markers of the disease that could help with early diagnosis are needed to improve prognosis.
21.01.2014 Boehringer Ingelheim has altered its joint development programme with Zealand Pharma in diabetes and obesity.
With immediate effect, Zealand Pharma will advance the dual-acting Glucagon/Glp-1 receptor agonist ZP2929, which is in Phase I development, independently of Boehringer Ingelheim. Instead, Boehringer will select another lead compound to be advanced for the treatment of type 2 diabetes and/or obesity within the partnership, under the same financial terms.
Under the collaboration agreement, signed between Zealand and Boehringer Ingelheim in June 2011, the collaboration provides for payments to Zealand upon the achievement of pre-defined development, regulatory and commercial milestones for the lead glucagon/GLP-1 dual-acting agonist advanced through development under the collaboration. Furthermore, Zealand is entitled to additional milestones if supplementary compounds discovered under the collaboration are advanced through development, and also to tiered royalties that range from high single to low double digits on global sales of products under the agreement. In the partnership, Boehringer Ingelheim finances all development, manufacturing and commercial activities and Zealand retains co-promotion rights in Scandinavia.
Commenting on this announcement, David Solomon, President and Chief Executive Officer of Zealand Pharma, said: “Our collaboration with Boehringer Ingelheim has been fruitful and we both continue to share excitement and strong commitment as to the potential of dual-acting glucagon/GLP-1 agonists as a unique and promising new approach to delivering better healthcare solutions to patients with diabetes and/or obesity. However, on ZP2929 we have differed in our views regarding the appropriate way forward in the development of this drug candidate. As a consequence, we have agreed with Boehringer Ingelheim that Zealand will retain the full control over the programme, leaving us the opportunity to apply our unique peptide drug capabilities to its continuation.“
20.01.2014 New data suggest that Prosensa’s DMD drug drisapersen may work in a subgroup despite a failed Phase III study.
Currently there is no treatment against the muscle wasting disease Duchenne muscular dystrophy, which is why GlaxoSmithKline entered into an agreement with Prosensa in 2009, after its RNA drug appeared to restore activity of the defective dystrophin gene by inducing exon 51 skipping in the largest known subpopulation of Duchenne Muscular Dystrophy (DMD) patients. However, a Phase III trial which kicked off in 2010 to show that the drug can help affected children to walk a longer distance in a six-minute walk test (6MWT) provided no significant difference between those who took drisapersen and those who took placebo. So, GSK terminated its cooperation with the Dutch company Analysts at Leerink said the fact GSK had handed back rights suggested that pooling and sub-group analyses had failed to provide strong enough evidence to justify a filing for approval.
Four days later, the Dutch firm, which is financed until mid-2015, announced they would consider further developing the drug, which has FDA breakthrough status, after additional data showed the treatment could slow the progression of the disease, news which sent its shares up 30 percent. According to Prosensa’s Chief Executive Hans Schikan, "these data encourage us to engage patient groups, clinical experts and regulators to explore a path forward for drisapersen, which includes the possibility of re-dosing." With data from more than 300 patients, Prosensa has the largest clinical data set in DMD. In order to advance the general understanding of DMD, Prosensa said it will make certain data from the drisapersen clinical programme available to the scientific community. Furthermore it is also exploring potential stratification biomarkers.
A new subset analysis, which focuses on outcomes in DMD boys seven years or younger and those over seven years old as measured by the six-minute walk test (6MWT), gives new hope. In all studies, a treatment difference was seen in the younger patient population. Notably, the preliminary analysis of the 96-week extension data from those participating in the Phase 3 DMD114044 (DEMAND 3) study shows a 49-metre difference between those on continual treatment and those who had been on placebo for 48 weeks followed by active drug. Those previously participating in the DMD114117 study (DEMAND 2) showed a 52-metre difference at 96 weeks. Key safety findings are consistent with previous observations. Schikan concluded: "We will continue to work closely with patient groups, clinical experts and regulators to ensure that we leave no stone unturned to bring treatments to boys affected by DMD."
17.01.2014 Dutch researchers have discovered how liver macrophages can help prevent metastases.
In the current issue of JCI (10.1172/JCI66776), the Dutch-Canadian research team headed by Marjolein van Egmond from VU University Medical Center, Amsterdam, report that so-called Kupffer cells in the liver are activated by therapeutic antibodies to remove tumour cells. According to the researchers, the process, dubbed antibody-dependent phagocytosis (ADPh), could be used to capture the dangerous residual tumour cells in the blood stream that support cancer recurrence and metastases.
Within a murine model of colorectal cancer, using intravital microscopy, they discovered that in the absence of mAbs, Kupffer cells sampled tumour cells. However, this sampling was not sufficient for elimination. By contrast, anti-tumour mAb treatment resulted in rapid phagocytosis of tumour cells by Kupffer cells, dependent on the high-affinity IgG-binding Fc receptor (FcγRI) and the low-affinity IgG-binding Fc receptor (FcγRIV). Uptake and intracellular degradation were independent of reactive oxygen or nitrogen species production.
Importantly, ADPh prevented the development of liver metastases. In the absence of tumour-specific mAbs approximately 80% of tumour cells came into contact with Kupffer cells, increasing to approximately 90% after mAb treatment. Surprisingly, this modest difference completely prevented liver metastases development. Tumour cell capture and therapeutic efficacy were lost after Kupffer cell depletion. The researchers conclude that macrophages play a prominent role in mAb-mediated eradication of tumour cells. These findings may help to optimise mAb strategies for patients with cancer by helping to enhance macrophage recruitment and activity. .
16.01.2014 UK researchers have succeeded in repairing a gene defect that causes loss of eyesight.
In The Lancet, the team headed by Robert E MacLaren from the University of Oxford reports that delivery of an intact copy of the CHM gene by an adeno-associated virus (AAV) into the eye improved the sight of patients with Choroideremia. This heritable disorder affects an estimated 1 in every 50,000 people and causes progressive loss of vision due to degeneration of the choroid, retinal pigment epithelium and the retina. There is currently no treatment available to stop the process that leads to complete blindness by middle age.
MacLaren and colleagues assessed the effect of gene therapy on retinal and visual function in six patients aged 35-63 years with different stages of choroideremia. They injected patients' retinas with a genetically engineered adeno-associated virus (AAV) to deliver a corrective copy of the gene into the appropriate part of the eye in order to halt photoreceptor cell death. The treatment caused no harm and resulted in improvements in subjective measurements of vision. Six months after delivery of the gene, all patients recovered their visual acuity from before the procedure, and two patients showed substantial improvements in quality of sight, with one reading over three additional lines on an eye chart. Importantly, the patients developed increased sensitivity to light, compared to a loss in sensitivity in the untreated eyes.
Findings from the phase 1 trial support further development of the gene therapy that may also be useful for other more common genetic causes of blindness, including degenerative diseases of old age, such as macular degeneration, and inherited defects like retinitis pigmentosa. "This is first time that gene therapy has been used to treat patients with normal visual acuity before the onset of clinically significant retinal thinning. Our findings hold great promise for gene therapy to prevent loss of sight in other retinal diseases such as age-related macular degeneration." said Mc Laren.
15.01.2014 German Bayer invests US$25.5m upfront to gain marketing rights for a new antibody drug against wet AMD from Regeneron.
Bayer is set to build on the success of its partnership with the US antibody expert Regeneron in the development of the potential wet-AMD blockbuster Eylea (aflibercept). The company will pay US$25.5m upfront to Regeneron for licensing an antibody in the same indication but with another target, the Platelet Derived Growth Factor Receptor beta (PDGFR-beta). The goal is tocombine the VEGF blocker Eylea, which is expected to achieve peak sales of US$2m.
According to both firms, pre-clinical data suggest that co-targeting of PDGFR-beta and VEGF can be advantageous over inhibiting VEGF alone as AMD therapy. Wet AMD develops when blood vessels damage macular cells. Without treatment, vision can deteriorate within days.
Under the agreement, the companies will be sharing the development costs and profits, with exception of the US market, where Regeneron will benefit from full commercialisation rights and returns. Regeneron can earn up to $40m in option and milestone payments through regulatory approval from Bayer. Clinical trials are expected to begin early next year.
14.01.2014 Sanofi will boost the orphan drug pipeline of its subsidiary Genzyme. In a US$700m deal the firm snaps up three programmes from Alnylam.
With its investment and a 12% stake in Alnylam Pharmaceuticals, Genzyme gets an option on all of Alnylam's medicines for rare genetic diseases. Alnylam's patisiran, a siRNA drug that fights transthyretin-mediated amyloidosis(ATTR) in patients with familial amyloidotic polyneuropathy, provided positive Phase II results in November. The RNA drug blocked 85% of the expression of the disease-causing TTR protein and will now be advanced to Phase III testing as the first ever siRNA drug. In addition, Sanofi has acquired the development and world-wide marketing rights to three other orphan drugs, according to the French pharma giant.
Sanofi is buying the Alnylam stake for about US$80 a share, a 21% premium over Alnylam's closing share price on Friday, 10 January. Alnylam said it will use the money to finance the acquisition of Sirna from Merck&Co, for which it agreed to payUS$25m in cash and $150m in stock.
In 2012, Sanofi and Alnylam formed a partnership to develop and market patisiran in Japan and the Asia-Pacific region, where the disease is disproportionately common. Under the new deal, Sanofi will sell the drug in all markets outside North America and Western Europe, according to the statement.According to market intelligence Evaluate, the market for orphan drugs is set to grow at twice the pace of the whole pharmaceutical sector, to US$127bn by 2018 from US$83bn in 2012.