Cristiana Bernini, Autore a NCF International

Agreements to exploit gene editing techniques

Business

Cristiana Bernini

-

19 December 2016

The new collaboration agreements signed between Germany-based Evotec and the life science business of Merck will combine Merck’s portfolio of genome editing technologies with Evotec’s versatile screening platforms and disease expertise. Merck’s comprehensive collection of genetic reagents – such as viral CRISPR and shRNA libraries – will be used to enable new target discovery programmes using Evotec’s capabilities for phenotypic screening in primary and induced pluripotent stem (“iPS”) cells, as well as its in vivo disease models.

According to Mario Polywka, chief operating officer of Evotec, together with the recent licensing of the CRISPR-Cas9 gene editing technology, these agreements with Merck further strengthen the company’s offering in the area of target identification and validation. “With this we provide more value to joint clients by a one-stop-shop solution for this innovative drug discovery segment”, said Dr Polywk

New nanotechnology centre in Brasil

Business

Cristiana Bernini

-

19 December 2016

0

The improvement of the bioavailability, efficacy and safety profile of oral therapeutic medicines through nanotechnology is the goal of the new collaboration signed between Ferring Pharmaceuticals and Brasil-based Aché Laboratórios Farmacêuticos. According to the companies, potential benefits of the operation might include a reduction of adverse effects, increased patient adherence to treatment and more convenient dosing. From 2017, the joint R&D centre and programme Nanotechnology Innovation Laboratory Enterprise (NILE) will be housed at Aché’s R&D centre in São Paulo, Brazil, funded by Ferring and Aché and governed by a joint steering committee.

The exploitation of nanotechnology as a delivery system for future medicines through programmes designed to match each company’s therapeutic needs will be the core activity of the centre. Peptides and proteins in reproductive health, gastroenterology and urology will represent the main focus for Ferring, while the initiative will represent a strategic platform to accelerate new therapeutic entity developments for Aché.

Acquisition in the hematologic and inflammatory area

Business

Cristiana Bernini

-

19 December 2016

0

Acquisition in the hematologic and inflammatory area

Novartis announced the acquisition of Selexys Pharmaceuticals; the deal comes as a consequence of the positive results obtained during the SUSTAIN study, a phase 2 trial evaluating the use of SelG1, an anti-P-selectin antibody, in the reduction of vaso-occlusive pain crises in patients with sickle cell disease (SCD). This hereditary blood disorder is characterized by sickle-shaped red blood cells and it represents a life-long disease with many forms that can range in clinical severity from asymptomatic to life-threatening. “Sickle cell disease affects millions of people around the world and there are limited therapies available for treatment of vaso-occlusive pain crises, a very common complication of the disease,” said Bruno Strigini, CEO of Novartis Oncology.

“With this acquisition, Novartis is able to leverage its leadership in haematology research to advance development of a potential new treatment option for patients living with this debilitating condition.” Terms of the deal could total up to $665 million in upfront, acquisition and milestone payments.

Transfer of the Hyafil Centre completed

Business

Cristiana Bernini

-

19 December 2016

0

The French biotechnology company Oncodesign announced the effective transfer of François Hyafil Research Centre (FHRC) from GSK and the appointment of two new activity directors, after the agreement for its acquisition signed in September 2016. The facilities have a total surface of 11,000m² and have been largely rebuilt as new in 2010. The deal included scientific equipment and the team of 57 employees, 47 of which are highly qualified scientists specialising in drug discovery. The transfer was accompanied € 35 million to be paid by GSK to Oncodesign over four years, subject to the continued employment of the transferred employees during this period

Dr Fabrice Viviani, will be the new Head of FHRC and Oncodesign’s Experimentation Director, while Dr Alexis Denis will assume the role of Discovery Director. The Executive Committee of the company is chaired by Philippe Genne. They will work under the direction of Oncodesign’s Chief Scientific Officer, Jan Hoflack.

New manufacturing plant for Dengue vaccine

Business

Cristiana Bernini

-

19 December 2016

0

New manufacturing plant for Dengue vaccine

Takeda Pharmaceutical Company announced the investment of more than € 100 million to build a new manufacturing plant for its dengue vaccine candidate in Singen, Germany. The investment will reinforce the company’s global vaccine strategy in general, and dengue in particular, according to Dr. Thomas Wozniewski, Global Manufacturing & Supply Officer at Takeda. “Our colleagues in Singen have vast experience in lyophilisation technology, which is key for the manufacturing process of Takeda’s dengue vaccine finished product,” he noted. The new facility should be ready for production in 2019.

Thomas Wozniewski, Global Manufacturing & Supply Officer at Takeda

Takeda’s tetravalent dengue vaccine candidate (TAK-003) is based on a live-attenuated dengue serotype 2 virus (DENV-2), which provides the genetic ‘backbone’ for all four vaccine viruses. The vaccine aims to support the protection of populations and individuals at risk for dengue across geographies whether or not they have had previous exposure to dengue virus, including children and adults, travelers and those living in endemic areas. The phase 3 double-blind, randomized, placebo-controlled trial TIDES is now enrolling approximately 20,000 healthy children between the ages of four and 16 years living in dengue-endemic countries in Latin America and Asia.

GE Healthcare enters orphaned IP market

Business

-

28 November 2016

0

GE Healthcare has announced the expansion of its consulting business through the acquisition of a 20% stake in global venture management company Pilot Lite Ventures (PLV). The final goal of the operation is to extend GE’s consulting business beyond hospitals and social care to life sciences companies and to enter into the global market of unexploited healthcare and wellness R&D, orphaned IP and early-stage technology, a sector with an estimated value of $28 billion. Financial terms of the deal were not disclosed; GE has the option to increase its stake in future.

London-based Pilot Lite Ventures has introduced the new concept of “venture management. The company collaborates with major corporates to validate, launch and commercialize new ventures, stranded IP, products and services. PLV activities are focused on translating early-stage innovations – often suffering for disinvestments because of corporates’ changes of strategy or lack of capital allocation – into commercially viable products and investable portfolios. Its activities will now be synergistic to the GE Healthcare Partners’ ones, more focused on analytics-based consulting solutions to health and social care organisations.

The eight stage “venture management” process de-risks the initial ‘white space’ origination of IP and then accelerates its journey to market as well as into new business models. According to Mike Anstey, CEO of PLV, “venture management” delivers accelerated market penetration and first revenues, not more paperwork and strategy. “Big evolving markets like healthcare have big evolving problems. Pilot Lite has a proven, systemic approach to commercializing IP and innovation, including putting specialist teams on the ground to manage new or previously-retired commercial ventures for major corporates. Adding this unique solution set to our offering will enable us to better meet our clients’ needs and to differentiate GE Healthcare Partners from traditional consultancy models”, said John Deverill, Managing Partner at GE Healthcare Partners.

Parkinson’s disease: results from a Phase 1 study against alpha-synuclein, safe and well tolerated

Trials

Cristiana Bernini

-

25 October 2016

0

AFFiRiS AG have recently announced the results of AFF008A, a Phase 1 clinical trial to assess boost immunizations with AFFITOPE^® PD01A, an active vaccine against Parkinson’s disease (PD). The data have of the study that was founded by a $1.04 million grant from The Michael J. Fox Foundation for Parkinson’s Research, have been presented at the Poster Tour of Leading Abstracts at the 4th World Parkinson Congress in Portland on September. The “boost” study AFF008A was designed to assess one boost immunization with AFFITOPE^® PD01A per patient with regard to safety/tolerability and immunological and clinical activity in those patients who had already received the vaccine (four “priming” vaccinations at four-week intervals) within the first-in-man clinical study AFF008. Six PD patients on best medical care, including standard symptomatic medication, served as a comparison group. In the “boost” study, two different doses of AFFITOPE^® PD01A (15 µg and 75 µg) were again safe and well tolerated, meeting the primary endpoint of the trial.

The study

Patients belonging to the low-dose group of AFF008 were randomized in two equally distributed groups receiving either 15 µg or 75 µg AFFITOPE^® PD01A. The same was done with patients of the AFF008 high-dose group, in order to allow for evaluation of four different vaccination schedules.

Across all patients, no antibody concentration limiting toxicity was observed. Adverse events were similar across all five groups except injection site reactions, which only occurred in the active treatment groups, and psychiatric disorders, reported at a lower rate in the active groups. All of the 28 patients completed the study and received all planned vaccinations. Only one serious adverse event was reported, which was classified as being not related to AFFITOPE^® PD01A administration. An immune response against AFFITOPE^® PD01A was seen in 19 of 22 (86%) of vaccinated patients and 12 of 19 (63%) of these responders generated aSyn-specific serum antibodies. The immune response sustained throughout the entire observation period of 24 weeks. Patients on low dose and then high dose had a clear immunological boost. This data supports that further dose and scheduling may significantly influence antibody titer/concentration and further studies need to be performed. Additionally, vaccine-induced antibodies were detectable in cerebrospinal fluid. This induction of antibodies against aSyn supports the concept of the principle of AFFiRiS’ proprietary therapeutic vaccine. The next study, AFF008AA, is focusing primarily on the long-term safety and, in addition, on the assessment of the immunological and clinical effects of a second boost vaccination (“reboost”). Recruitment of patients for AFF008AA has been completed; results are expected in Q2 2017.

Somatic cell therapy product for leukaemias and lymphomas

Cristiana Bernini

-

25 October 2016

0

The European Commission granted a marketing authorization valid throughout the European Union for Zalmoxis on 18 August. Zalmoxis is a medicine used as an add-on treatment in adults with leukaemias and lymphomas who have received a haploidentical haematopoietic stem cell transplant. Zalmoxis is an advanced therapy medicine called a ‘somatic cell therapy product’. It contains T cells from the HSCT donor that have been genetically modified to include a ‘suicide gene’. In detail Zalmoxis contains allogenic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor (ΔLNGFR) and the herpes simplex I virus thymidine kinase (HSV-TK Mut2).

Because the number of patients undergoing haploidentical HSCT is low, in 2003 it was designated as an ‘orphan medicine’.

Zalmoxis is prepared for use in a specific patient. It is given 21 to 49 days after transplantation, but only if the transplant has not already restored the patient’s immune system and if the patient has not developed graft-versus-host disease. It helps the patient to build up their immune system and so helps to protect them from infections. However the T cells in Zalmoxis can sometimes attack the patient’s body, causing graft-versus-host disease. The T cells in Zalmoxis have a suicide gene, which makes them susceptible to the medicines ganciclovir and valganciclovir. If the patient develops graft-versus-host disease, ganciclovir or valganciclovir is given, which kills the T cells that have the suicide gene thereby treating the disease and preventing its further development.

Zalmoxis has been investigated in a main study involving 30 patients who had haploidentical HSCT for serious blood cancers. In this study, Zalmoxis was not compared with any other treatment. The main measure of effectiveness was restoration of the immune system as measured by blood levels of T cells. 77% of the patients receiving Zalmoxis (23 out of 30) had their immune systems restored. Graft-versus-host disease occurred in 10 patients who were then given ganciclovir or valganciclovir, either alone or in combination with other medicines. All 10 patients recovered from graft-versus-host disease.

Data from the main study were also combined with data from a second ongoing study, and survival rates for 37 patients treated with Zalmoxis (23 from the main study and 14 from the ongoing study) were compared with rates from a patient database of 140 patients who have undergone haploidentical HSCT in the past. The number of patients who survived after one year was 51% for patients who received Zalmoxis compared with 34 to 40% for patients who did not receive Zalmoxis.

Zalmoxis has been given ‘conditional approval’. This means that there is more evidence to come about the medicine, which the company is required to provide.

There is an ongoing study in high-risk acute leukaemia patients. The study will compare haploidentical HSCT followed by treatment with Zalmoxis with haploidentical HSCT containing T cells followed by treatment with cyclophosphamide (a medicine to prevent graft-versus-host disease) and with haploidentical HSCT without T cells.

Eluxadoline for the treatment of irritable bowel syndrome with diarrhoea

Drug Delivery

Cristiana Bernini

-

25 October 2016

0

On 19 September the European Commission granted a marketing authorisation valid throughout the European Union for the active substance eluxadoline (Truberzi). Eluxadoline acts on the digestive system. It is used for the treatment of adults who have irritable bowel syndrome with diarrhoea.

Eluxadoline is an opioid receptor agonist: it attaches to opioid receptors and acts like the body’s natural opioids to calm down waves of contractions along the digestive system. This causes food to remain in the gut for longer, increasing the absorption of fluids and so reducing diarrhoea. Because eluxadoline is not absorbed into the blood and distributed around the body, its effects are largely confined to the gut.

The drug was evaluated in two main studies compared with placebo involving over 2,400 patients with irritable bowel syndrome with diarrhoea. The study takes over 26 weeks of treatment during which patients kept a daily record of their symptoms. Effectiveness was measured as an improvement of over 30% in abdominal pain combined with an absence of very loose stool.

In the first study effectiveness was shown in 29% (125 out of 426) of patients taking eluxadoline 100 mg twice a day compared with 19% (81 out of 427) in patients taking placebo. In the second study symptoms improved in 33% (125 out of 382) of patients taking eluxadoline 100 mg twice a day compared with 20% (77 out of 382) of patients taking placebo.

Constipation, nausea and abdominal pain was the most common side effects, while serious one include pancreatitis and sphincter of Oddi spasm

The Agency’s Committee for Medicinal Products for Human Use (CHMP) considered that the benefits of the drug are modest but there is an unmet need for treatments of irritable bowel syndrome with diarrhoea. Side effects were mainly limited to the digestive system and mostly mild. The Committee therefore decided that Truberzi’s benefits are greater than its risks and recommended that it be approved for use in the EU.

Endometriosis: Phase 2B EDELWEISS study on GnRH antagonist

Trials

Cristiana Bernini

-

24 October 2016

0

The Swiss biopharmaceutical company ObsEva SA recently announced randomization of the first patient EDELWEISS, a Phase 2b clinical study of OBE2109 for the treatment of endometriosis. Endometriosis is a painful, debilitating condition that affects approximately 176 million women globally between the ages of 15 and 49 and is a leading cause of infertility. OBE2109 is orally administered gonadotropin-releasing hormone (GnRH) antagonist that has been tested in more than 150 Japanese patients with endometriosis with interesting results on reductions of endometriosis-associated pelvic pain, analgesic use and bleeding days.

EDELWEISS is a double-blind, placebo-controlled and dose-ranging study that will assess the efficacy and safety of the novel GnRH antagonist in patients with endometriosis and pelvic pain. The study will be conducted in North America (46 center) and Europe (15 centers), on more or less 330 endometriosis patients who will be treated daily for 24 weeks, with an option to receive OBE2109 for another 28 weeks and then a period of treatment-free 24 week.

Primary endpoint of the study: menstrual and non-menstrual pelvic pain.

About OBE2109 and GnRH

OBE2109 is a novel, orally administered GnRH receptor antagonist with a potentially best-in-class profile in late-stage clinical development for the treatment of pain associated with endometriosis and heavy menstrual bleeding associated with uterine fibroids. OBE2109 acts by binding to and blocking the GnRH receptor in the pituitary gland, ultimately reducing estrogen production by the ovaries. Through previously reported results from this class of drugs and sophisticated pharmacological modelling, it has been established that maintaining estradiol within a specific target range provides the optimal balance between reducing the pain symptoms associated with endometriosis while mitigating bone density loss associated with excessive estradiol suppression.6 In Phase 2a studies conducted in Japan, patients treated with OBE2109 were observed to have a reduction of endometriosis-associated pain, analgesic use and bleeding days. ObsEva licensed OBE2109 from Kissei in late 2015 and retains worldwide commercial rights, excluding Asia, for OBE2109.

Cristiana Bernini

The study

About OBE2109 and GnRH

Newsstand