24 October 2019

NIH and Gates Foundation fund sickle cell and HIV research

The National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation have committed $100m each to support the development of gene-based cures for sickle cell disease (SCD) and HIV.

The partners aim to ensure the cures are affordable and accessible, even in low-resource regions and areas profoundly affected by the diseases.

Gene therapies have already been developed to treat blindness and some leukaemia types. However, these treatments are considered expensive and can be given only in hospitals with resources.

While SCD is an inherited disease and HIV is an acquired infectious disease, gene-based cures are possible for both conditions.

The companies intend to bring safe, effective and durable gene-based cures into clinical trials for SCD and HIV in the US and relevant sub-Saharan African countries within the next seven to 10 years.

NIH director Francis Collins said: “This unprecedented collaboration focuses from the get-go on access, scalability and affordability of advanced gene-based strategies for sickle cell disease and HIV to make sure everybody, everywhere has the opportunity to be cured, not just those in high-income countries.”

The research will focus on treatments that deliver medication to the target site, including mutations in haemoglobin responsible for SCD and the proviral DNA reservoir in HIV patients.

Bill & Melinda Gates Foundation global health program president Trevor Mundel said: “By working with the NIH and scientists across Africa, we aim to ensure these approaches will improve the lives of those most in need and bring the incredible promise of gene-based treatments to the world of public health.”

The organisations will also invest in other research projects working on SCD and HIV cures.

Of the 38 million HIV patients worldwide, 95% are in developing countries, including 67% in sub-Saharan Africa, 50% of whom remain untreated.

Furthermore, estimations show that approximately 15 million babies will be born with SCD over the next 30 years globally. Around 75% of the affected will be in sub-Saharan Africa.

24 October 2019

Novartis partners with Pliant Therapeutics for fibrosis assets

Novartis has signed a collaboration and licence agreement with Pliant Therapeutics to develop and commercialise a preclinical asset, PLN-1474, designed to inhibit the αVβ1 integrin.

The agreement also covers global exclusive licence for up to three additional integrin targets.

PLN-1474 treats nonalcoholic steatohepatitis (NASH)-related liver fibrosis, which could cause complications, including cirrhosis and liver failure.

αvβ1 is an integrin triggers TGF-β, which regulates hepatic fibrosis. With selective αVβ1 inhibition, PLN-1474 demonstrated a significant reduction of fibrosis in live models of human tissue.

Pliant expects to apply by the end of the year to seek approval from the US regulator.

Pliant Therapeutics president and CEO Bernard Coulie said: “Pairing Pliant’s leading integrin biology and drug discovery capabilities with Novartis, a world-leader with one of the broadest pipelines investigating mono and combination therapies for liver diseases including NASH, will support our goal of developing novel therapies for fibrotic diseases and potentially bring meaningful treatment options to patients.”

Initially, Novartis will pay $80m to Pliant, including an upfront payment and equity investment. The company will also fund research and development activities carried out by Pilant as part of the deal.

Pliant will develop PLN-1474 through Phase I. Novartis will be responsible for future development, manufacturing and commercialisation.

Under the agreed terms, Pliant is also eligible for additional payments based on development, regulatory and commercial milestones. Furthermore, the company may receive tiered royalties on product sales.

The deal is subject to customary closing conditions and antitrust clearance.

Last month, Novartis signed a collaboration and exclusive option agreement with IFM Therapeutics to develop immunotherapies for severe inflammatory and autoimmune disorders.

23 October 2019

Takeda licenses coeliac disease therapy from COUR

Takeda Pharmaceutical has obtained exclusive, worldwide rights for the development and commercialisation of COUR Pharmaceutical Development’s drug candidate for coeliac disease.

CNP-101 / TAK-101 is an investigational immune modifying nanoparticle made of gliadin proteins. It is designed using COUR’s immune tolerance platform to target the immune response associated with coeliac disease.

Coeliac disease is an autoimmune disorder characterised by gluten ingestion resulting in inflammation and damage in the small intestine. Patients typically manage their symptoms by avoiding gluten.

However, the disease currently lacks treatments for patients whose symptoms continue.

Takeda Pharmaceutical Gastroenterology therapeutic area unit head Asit Parikh said: “Our collaboration with COUR has shown, for the first time, that it is possible to induce specific immune tolerance to a foreign antigen in autoimmune diseases such as coeliac disease.

“With our expertise in inflammatory diseases, Takeda is well-positioned to further develop TAK-101 in pursuit of providing the first approved treatment option for patients with coeliac disease.”

Takeda exercised its option to buy the licence to TAK-101 comes from results of a randomised, double-blind, placebo-controlled clinical trial that evaluated intravenous formulation of the drug candidate given on days one and eight.

The study involved 34 patients who took a gluten challenge at seven days following the second administration. During the trial, participants received 12g of gluten each day for three days, followed by 6g per day for 11 days.

The primary endpoint of the trial was the change in interferon-gamma (IFN-γ) spot forming units (SFUs) from baseline at day 6 post-gluten. It was measured using a gliadin-specific enzyme-linked immunospot (ELISpot) assay for gluten-specific systemic T-cell activation.

Of the total participants, six discontinued because of gluten symptoms, while the remaining 28 completed the 14-day gluten challenge.

The trial met the primary endpoint, where TAK-101 showed a mean change of 2.10 in IFN-γ ELISpotSFUs from baseline, compared to 17.57 in the placebo arm.

Takeda plans to launch a dose-ranging study of TAK-101 in celiac disease patients on a gluten-free diet. Data from this study is expected to inform future registrational trials.

The company will pay up to $420m to COUR in the future, along with sales royalties on commercialised therapies resulting from the licence.

23 October 2019

Zealand Pharma to acquire Canada’s Encycle Therapeutics

Danish biotechnology firm Zealand Pharma has agreed to buy all outstanding shares and intellectual property of Canada-based Encycle Therapeutics.

Encycle Therapeutics provides technology to synthesise macrocyclic peptides with drug-like properties. It pipeline comprises a pre-clinical asset, ET3764.

ET3764 is an oral, peptide drug designed to target integrin alpha-4-beta-7 associated with the pathogenesis of inflammatory bowel disease (IBD).

The mode of action of the target has been validated in IBD by vedolizumab, an alpha-4-beta-7 integrin inhibitor.

The terms of the agreement cover all rights to develop and commercialise ET3764. However, the deal does not include any infrastructure or personnel costs.

Zealand expects the acquisition to boost its presence in peptide therapeutics and gastrointestinal diseases fields. It also gains access to Encycle’s screening library of nearly 5,000 peptide macrocycles with potential across various therapeutic areas.

The company could use its peptide development expertise to identify additional targets in the screening library.

Zealand Pharma president and CEO Emmanuel Dulac said: “Encycle has demonstrated the significant potential of its innovative peptide chemistry, and have remained focused on benefitting patients by creating orally-delivered therapies. We look forward to continuing progress by leveraging Zealand’s established leadership in peptide drug development.”

Under the agreement, Zealand will potentially pay $80m in one-time contingent value rights, including $10m in earn-outs at the successful completion of Phase II clinical trial.

All earn-outs may be paid in cash or Zealand equity, related to ET3764 and based on select development, regulatory and commercial milestones in the future.

Encycle is also eligible for royalties on net sales of the asset.

Encycle Therapeutics president and CEO Dr Jeffrey Coull said: “Encycle has been working on proprietary peptide macrocycles for several years, and our research shows that they have enormous potential to target protein-protein interactions, which are largely intractable to small molecule and biologic modulation.

“We are pleased to transfer our technology into the successful development capabilities of Zealand Pharma, to realise its full therapeutic potential.”

22 October 2019

Multiple drug companies settle opioid litigation in Ohio for $260m

Teva Pharmaceutical and three drug distributors, McKesson, Cardinal and AmerisourceBergen, have agreed to pay a total of $260m to settle opioid litigation in Cuyahoga and Summit counties of Ohio, US.

The settlement was signed hours before the companies were set to face court trial.

As part of the agreement, the drug distributors will pay $215m to resolve the first track of the multi-district litigation.

In a joint statement, McKesson, Cardinal and AmerisourceBergen said: “While the companies strongly dispute the allegations made by the two counties, they believe settling the bellwether trial is an important stepping stone to achieving a global resolution and delivering meaningful relief.

“The companies expect settlement funds to be used in support of initiatives to combat the opioid epidemic, including treatment, rehabilitation, mental health and other important efforts.”

Meanwhile, Teva will make a $20m payment in cash over three years. The company will also provide $25m worth opioid treatment called Suboxone (buprenorphine naloxone) to help people with addiction.

The agreement is expected to pave the way for a $48bn deal to settle approximately 2,600 opioid lawsuits pending across the country.

The company has reached an agreement with attorneys general from North Carolina, Pennsylvania, Tennessee and Texas as part of a global settlement framework.

The proposed global resolution will see Teva donate buprenorphine naloxone tablets worth around $23bn. The provided quantity is expected to cater to the current estimated patient need in the US over the coming ten years.

Furthermore, the company will provide up to $250m over ten years.

A statement from Teva read: “The company is pleased to positively contribute to solving the nationwide opioid epidemic. Teva has consistently committed to complying with all laws and regulations regarding its manufacture and sale of opioids. Neither settlement includes an admission of liability.”

22 October 2019

Verseau Therapeutics launches with focus on immunotherapies

Verseau Therapeutics has launched to develop immunotherapies that act as checkpoint modulators of macrophages, inducing an immune response against cancer.

The company received a $50m investment from 3SBio, 20 / 20 HealthCare Partners, Yonghua Capital, The Mark Foundation for Cancer Research, InHarv Partners, Highlight Capital and Alexandria Venture Investments.

Verseau Therapeutics will use the funds to advance macrophage checkpoint modulator (MCM) programmes into the clinic.

Macrophages exhibit a variety of functional responses such as pro-inflammatory and anti-inflammatory immune responses.

The company has licensed the siRNA delivery technology from the MIT laboratories.

It intends to leverage the technology, among similar delivery approaches, with its all human translational system to identify and validate macrophage targets.

The company’s pipeline comprises a PSGL-1 candidate, which reprogrammes macrophages to a pro-inflammatory state, stimulates T-cells and attracts other immune cells to produce a coordinated anti-tumour response.

When tested in patient-derived PD-1 responsive and non-responsive tumours, PSGL-1 antibodies show enhanced inflammatory response compared to existing immunotherapies.

Verseau Therapeutics co-founder and chief scientific officer Dr Tatiana Novobrantseva said: “Using our proprietary discovery and validation platform, we identified PSGL-1, an adhesion molecule that is highly expressed on tumour-associated macrophages across most tumour types, as the target of our first-in-class MCM programme.

“Our PSGL-1 MCM antibody is designed to reprogramme inhibitory tumour-associated macrophages into anti-cancer immune response stimulators. Verseau has validated more than two dozen targets amenable to different therapeutic modalities, including monoclonal antibodies.”

The company has collaborated with Chinese biotechnology firm 3SBio.

The partnership offers 3SBio exclusive rights to develop and commercialise MCM antibodies across all cancer indications in Greater China, including mainland China, Taiwan and Hong Kong, as well as Macau.

The agreement provides Verseau Therapeutics with all worldwide rights.

18 October 2019

Teva recalls Ranitidine medicines batches in UK

The Medicines and Healthcare products Regulatory Agency (MHRA) in the UK has announced that Teva’s subsidiary is recalling batches of Ranitidine medicines.

Ranitidine is indicated to treat ailments such as heartburn and stomach ulcers.

Teva UK recalled unexpired stock of 150µg and 300mg Ranitidine Effervescent Tablets over concerns of potential contamination with the N-nitrosodimethylamine (NDMA) impurity, linked to some cancers.

Healthcare professionals have been asked to cease the supply of the select batches and immediately return the stock to the supplier. MHRA has urged patients to continue with their medication.

Earlier this month, MHRA reported that GlaxoSmithKline (GSK) issued a recall of all unexpired stock of four types of Zantac, which contains ranitidine as the active substance, due to contamination concerns.

Regulatory authorities, including the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), are reviewing the potential contamination of ranitidine products.

MHRA inspections, enforcement & standards deputy director Dr Andrew Gray said: “We have asked companies to quarantine batches of potentially affected medicines whilst we investigate and we will take action as necessary, including product recalls where appropriate.

“We have also requested risk assessments from the relevant companies, which will include the testing of potentially affected batches.

“Currently, there is no evidence that medicines containing nitrosamines have caused any harm to patients but the agency is closely monitoring the situation and working with other regulatory agencies around the world.”

Cancer-causing contaminants, including NDMA, have been detected in various blood pressure and heart failure drugs since last year.

Last July, MHRA and Irish Health Products Regulatory Authority (HPRA) recalled all batches of valsartan-containing drugs produced by Dexcel Pharma and Accord Healthcare (Actavis Group).

17 October 2019

Positive results for ruxolitinib in graft-versus-host disease

Incyte Corporation has announced promising results for ruxolitinib in the Novartis-sponsored Phase III trial REACH2 of patients with steroid-refractory acute graft-versus-host disease.

Ruxolitinib met its primary endpoint in the trial of superior overall response rate (ORR) on day 28 of treatment, compared to best currently available therapy.

There were also no safety signals for ruxolitinib in REACH2, and the drug’s safety and tolerability profile were consistent with previous trials.

Full results for this JAK1 and JAK2 tyrosine kinase inhibitor will be presented at an upcoming medical meeting.

The US Food and Drug Administration (FDA) has already approved ruxolitinib for the same indication – steroid-refractory acute graft-versus-host disease – based on the results of the Phase II REACH1 trial, which had the same day 28 ORR primary endpoint.

The US is the remit of the drug’s developers Incyte, which calls the drug Jakafi. Novartis will be responsible for the development or commercialisation of ruxolitinib as Jakavi outside of the US.

Ruxolitinib is also being studied in the Phase III REACH3 study for steroid-refractory chronic graft-versus-host disease.

Novartis chief medical officer and head of global drug development John Tsai said: “As many as half of hematopoietic stem cell transplant recipients develop acute graft-versus-host disease.

“We are delighted that Jakavi showed such promise in this very difficult condition especially since few second-line treatment options exist. These impressive results will be part of our regulatory submissions seeking approval in Europe and other countries.”

Incyte group vice-president in targeted therapies Peter Langmuir said: “Graft-versus-host disease is a challenging and serious disease, and physicians around the world need access to therapies that can improve outcomes for patients.

“This positive result of the REACH2 study is excellent news for patients as it further reinforces the potential of ruxolitinib as a treatment option that can provide meaningful results for patients with steroid-refractory acute graft-versus-host disease.”

Ruxolitinib has also already been approved globally for a range of haematological indications, such as polycythaemia vera (PV), primary myelofibrosis (MF), post- polycythaemia vera MF or post-essential l thrombocythaemia MF.

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