COVID-19 Vaccine Development

AstraZeneca Under Fire for COVID-19 Vaccine Safety, Releases Trial Protocol

Following scrutiny over a potential patient side effect that prompted a clinical hold of its Phase III vaccine trial earlier this month, AstraZeneca revealed details of its large coronavirus vaccine trials on 19th Sep 2020, the third in a wave of rare disclosures by drug companies under pressure to be more transparent about how they are testing products that are the world’s best hope for ending the pandemic.

Experts have been particularly concerned about AstraZeneca’s vaccine trials, which began in April in the UK, because of the company’s refusal to provide details about serious neurological illnesses in two participants, both women, who received its experimental vaccine in Britain. Those cases spurred the company to halt its trials twice, the second time earlier this month.

The company’s protocol amendment 2 dated 17th Sep 2020, states that its goal is a vaccine with 50% effectiveness — the same threshold that the Food and Drug Administration (FDA) has set in its guidance for COVID-19 vaccines. To determine with statistical confidence whether the company has met that target, there will have to be 150 subjects infected with confirmed coronavirus among participants who were vaccinated or received placebo. The protocol anticipates that a safety board will perform an early analysis after there have been just 75 cases. If the vaccine is 50% effective at that point, it might be possible for the company to stop the trial early and apply for authorisation to release the vaccine for emergency use.

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Sanofi and GSK to Supply EU with up to 300 Million Doses of COVID-19 Vaccine

On 18th Sep 2020, Sanofi and GlaxoSmithKline (GSK) finalised an advanced purchase agreement with the European Commission (EC) for supply of up to 300 million doses of their COVID-19 vaccine candidate, following approval by regulatory authorities. Their vaccine candidate leverages Sanofi’s recombinant protein-based technology alongside GSK’s adjuvant technology, a Phase I / II clinical trial of the vaccine was initiated earlier in the month and a Phase III trial is scheduled to start by the end of the year.

Under terms of the agreement it will allow the purchase for all member states of the European Union (EU), which may donate reserved doses to lower- and middle-income countries. The EU will provide upfront funding to help scale-up the companies’ manufacturing capabilities in Europe. The antigen and final vaccine doses will be manufactured in Sanofi and GSK’s industrial sites in Belgium, Italy, Germany and France.

EC President von der Leyen stated: “With today’s contract with Sanofi-GSK, the European Commission shows once again its commitment to ensuring equitable access to safe, effective and affordable vaccines not only for its citizens but also for the world’s poorest and most vulnerable people. Agreements with other companies will be concluded soon and build a diversified portfolio of promising vaccines, based on various types of technologies, increasing our chances to find an effective remedy against the virus.”

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BioNTech to Acquire Novartis’ GMP Manufacturing Site to Expand COVID-19 Vaccine Production

On 17th Sep 2020, BioNTech announced signing a share purchase agreement with Novartis to acquire their Good Manufacturing Practice (GMP) certified manufacturing facility in Marburg, Germany. The site will expand BioNTech’s COVID-19 vaccine production capacity by up to 750 million doses per year, or over 60 million doses per month, once fully operational.

The company expects to produce up to 250 million doses of vaccine candidate BNT162b2 in the first half of next year, owing to the team, drug substance and drug product manufacturing capabilities at the Novartis facility. The facility has around 300 employees and is equipped to manufacture recombinant proteins, cell and gene therapies, along with cell culture labs and capabilities for viral vector production. Following regulatory approval, the site will begin the manufacturing of mRNA and the lipid nanoparticles (LNP) formulation for a COVID-19 vaccine in the first half of next year.

Dr. Sierk Poetting, Chief Financial Officer and Chief Operating Officer at BioNTech stated:” This acquisition reflects BioNTech’s commitment to significantly expanding its manufacturing capacity in order to supply a potential vaccine worldwide upon authorization or approval. We are working closely with Novartis to prepare for a smooth transition, and we look forward to welcoming the new members of our team and tapping into their impressive skills and expertise. From a strategic standpoint, the new site will bolster our vertically integrated business model with in-house manufacturing capabilities for mRNA manufacturing as well as vaccine formulation.”

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US Researchers Identify Tiny Biological Molecules to Neutralise SARS-CoV-2

On 14th Sep 2020, researchers University of Pittsburgh School of Medicine (UPMC) scientists reported in an article published in Cell that Ab8 which uses an antibody component ten times smaller compared to a full-sized antibody in its construct, was highly effective in preventing and treating SARS-CoV-2 infection in mice and hamsters.

The small size of the molecule rises its potential for diffusion in tissues to better neutralise the virus causing COVID-19, as well as enables alternative routes of administration, such as inhalation. it does not bind to human cells—a good sign that it won’t have negative side-effects in people. The tiny antibody component is the variable, heavy chain (VH) domain of an immunoglobulin, which is a type of antibody found in the blood. It was found by “fishing” in a pool of more than 100 billion potential candidates using the SARS-CoV-2 spike protein as bait. Ab8 is created when the VH domain is fused to part of the immunoglobulin tail region, adding the immune functions of a full-size antibody without the bulk.

John Mellors, Chief of the Division of Infectious Diseases at UPMC and Pitt stated: “Ab8 not only has potential as therapy for COVID-19, but it also could be used to keep people from getting SARS-CoV-2 infections,” said co- “Antibodies of larger size have worked against other infectious diseases and have been well tolerated, giving us hope that it could be an effective treatment for patients with COVID-19 and for protection of those who have never had the infection and are not immune.”

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COVID-19 Research and Therapeutic Development

R-Pharm’s COVID-19 Drug Coronavir Receives Regulatory Approval for Sale in Pharmacies

On 17th Sep 2020, the R-Pharm group of companies announced receipt of marketing authorisation (LP-006323) for COVID-19 prescription drug, Coronavir, to treat outpatients with mild to moderate infection. According to the marketing authorization, Coronavir has emerged as the first medicine for coronavirus infection in Russia to make it to pharmacies, becoming available to a broad population of out-patients.

Approval comes from the final data obtained from Phase III clinical trial performed in patients with mild to moderate Covid-19 in community and hospitalised settings. Data from the trial showed that in 168 COVID-19 patients Coronavir reduced median time to clinical improvement (using the WHO Ordinal Scale for Clinical Improvement) in infected patients by 4 days, and by 8 days in the cohort of out-patients. The drug demonstrated a favourable safety profile, most subjects tolerated the treatment well. Specific adverse effect related to the medication, predominantly mild and resolving after treatment completion.

Alexey Repik, R-Pharm board of directors Chairman stated: “Our common mission is to make this product with proven efficacy available to every patient in need, whether treated at a hospital or isolated at home”.

Mikhail Samsonov, R-Pharm medical department Director stated: “According to the clinical trial evidence, Coronavir, when administered in a timely manner early during the disease course, has demonstrated the best efficacy among all medicines used by now”.

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Eli Lilly Partners with Amgen for COVID-19 Antibody Therapies

On 17th Sep 2020, Eli Lilly and Amgen announced a global antibody manufacturing collaboration to increase the supply capacity available for Lilly’s COVID-19 therapy candidates. Lilly is currently testing several potential neutralising antibodies for the prevention and/or treatment of COVID-19 as either monotherapy or in combination. Under terms of the agreement, the companies will have the ability to quickly scale up manufacturing and global access to Lilly’s antibody therapies if one or more proven successful in clinical testing and receive regulatory approval.

Eli Lilly has reported positive proof-of-concept results from the BLAZE-1 clinical trial, which assessed SARS-CoV-2 neutralising antibody candidate LY-CoV555, to treat symptomatic COVID-19 in outpatients. An interim analysis found that the drug candidate decreased rate of hospitalisation.

Daniel Skovronsky, Lilly’s chief scientific officer and president of Lilly Research Laboratories stated: “Based on our initial clinical studies, we believe that virus neutralising antibodies, including LY-CoV-555, could play an important role in the fight against COVID-19. Increasing the manufacturing capacity for our neutralising antibodies through this collaboration with Amgen is a crucial next step, and together we hope to be able to produce many millions of doses even next year.”

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Verona Pharma Initiates Pilot Study of COVID-19 Inhaler in Hospitalised US Patients

On 8th Sep 2020, Verona Pharma, a clinical-stage biopharmaceutical company focused on respiratory diseases, announces the initiation of a pilot study to investigate the efficacy and safety of ensifentrine delivered via pressurised metered-dose inhaler (“pMDI”) formulation in US patients hospitalised with COVID-19. The study will evaluate the effect of ensifentrine on key outcomes in patients hospitalised with COVID-19, including facilitation of recovery from the viral infection, clinical status improvement and reduction in supplemental oxygen use and progression to mechanical ventilation.

Ensifentrine is a first-in-class product candidate that combines bronchodilator and anti-inflammatory activities in one compound. Clinical data from studies of ensifentrine in the treatment of other respiratory diseases have shown that it improved oxygenation, reduced inflammation in the lungs and enhanced mucus clearance.

David Zaccardelli, President and CEO of Verona Pharma, stated: “The need for effective COVID-19 treatments to reduce the disease burden is clear and we believe ensifentrine, with its novel mechanism of action, could help to improve patient outcomes. If the pilot study is successful, we are committed to progressing ensifentrine as a treatment for COVID-19 and, if approved, increasing supplies to meet public health needs.”

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Other Pharma Industry News

First-line Treatment with Merck’s Keytruda® Doubled Five Year Survival Rate

On 21st Sep 2020, Merck announced five-year survival results from Phase III KEYNOTE-024 trial, which demonstrated a sustained, long-term survival benefit and durable responses with Keytruda® versus chemotherapy as first-line treatment in patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express programmed death-ligand 1 (PD-L1) with no genomic tumor aberrations. At five years, the overall survival (OS) rate was twice as high for patients who received Keytruda®  (31.9%; n=154) versus chemotherapy (16.3%; n=151). The drug also reduced the risk of death by 38% versus chemotherapy, with a median OS of 26.3 versus 13.4 months. Results from the trial represent the longest follow-up and first-ever five-year survival data for an immunotherapy in a randomized Phase III study for the first-line treatment of NSCLC. Data from the trial was presented as a proffered paper at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 on 21st Sep 2020.

Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories stated: ““KEYTRUDA has become foundational in the treatment of metastatic lung cancer based on the sustained, long-term survival benefit demonstrated in our clinical trials. These new, first-of-their-kind five-year survival results from KEYNOTE-024 add to our understanding of the important role that KEYTRUDA now has in the treatment of lung cancer.”

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Vertex and Moderna Team Up in Gene-editing Therapies for Cystic Fibrosis

On 16th Sep 2020, Moderna and Vertex Pharmaceuticals announced a research collaboration and licensing agreement aimed at the discovery and development of lipid nanoparticles (LNPs) and mRNAs for the delivery of gene-editing therapies for the treatment of cystic fibrosis (CF). The three-year research partnership initially will focus on the discovery and optimization of novel LNPs and mRNAs that can deliver gene-editing therapies to cells in the lungs, enabling functional cystic fibrosis transmembrane conductance regulator (CFTR) protein to be produced. Under terms of the agreement, Moderna will undertake the discovery and manufacturing of LNPs and mRNA constructs encoding gene-editing endonucleases. Vertex will be responsible for supplying components of the gene-editing therapies for formulation into LNPs, followed by preclinical and clinical development and sale.

David Altshuler, Vertex’s Executive Vice President, Global Research and Chief Scientific Officer stated: “Vertex’s CFTR modulator therapies have the potential to treat the vast majority of CF patients and address the underlying cause of their disease. However, approximately 10 percent of patients do not produce any CFTR protein and so are unlikely to benefit from our existing medicines. Over the past 5 years, we have made important progress in our research efforts aimed at the creation of genetic therapies for CF, with the delivery of such therapies remaining the most significant technological and scientific challenge. The combination of Moderna’s unique expertise in the discovery and manufacturing of novel LNP delivery systems and mRNA technologies, combined with Vertex’s scientific, clinical and regulatory capabilities in CF, will accelerate the development of ground breaking genetic therapies for people with CF and supports our commitment to developing therapies for all people living with CF.”

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Takeda Opens New R&D Cell Therapy Manufacturing Facility

On 15th Sep 2020, announced the expansion of its cell therapy manufacturing capabilities with the opening of a new 24,000 square-foot Research and Development (R&D) cell therapy manufacturing facility at its headquarters in Boston, Massachusetts. The facility provides end-to-end research and development capabilities and will accelerate Takeda’s efforts to develop next-generation cell therapies, initially focused on oncology with potential to expand into other therapeutic areas.

The new facility will produce cell therapies for clinical evaluation from discovery through pivotal Phase IIb trials. The current facility is designed to meet all US., EU. and Japanese regulatory requirements for cell therapy manufacturing to support Takeda clinical trials around the world. It will be instrumental in building Takeda’s cell therapy capabilities and capacity to advance multiple next-generation oncology cell therapy platforms and programs with world-class collaborators

Takeda Pharmaceutical Oncology Therapeutic Area unit head Chris Arendt stated: “With three oncology cell therapy programmes in the clinic and two more targeted to enter the clinic in fiscal year 2021, we are working with urgency and purpose for patients. This new facility helps us rapidly scale our manufacturing capabilities so we can simultaneously advance multiple highly differentiated cell therapy programmes.”

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University of Edinburgh Launches Spin-Out Cellinta for Development of Gene Therapies for Cancer

On 15th Sep 2020, Cellinta Limited, a new private company focussed on targeting cancer stem cells with highly selective gene therapy born out of research from scientists at the University of Edinburgh, was officially launched following a successful fundraise led by SV Health Investors and joined by Cancer Research UK.

The funding will be used to develop a pipeline of ‘highly selective’ gene therapies targeting cancer stem cells in a variety of solid tumour types. It will draw on research led by Professor Steven Pollard at the University of Edinburgh, which delved into stem cell biology, synthetic biology and cancer genomics. The company has entered into a collaborative research agreement with the University and retains the option to license intellectual property developed from research conducted there.

Dr. Soraya Bekkali, Chief Executive Officer stated: “I am delighted to be leading such an exciting company. Cellinta’s approach offers the opportunity to deliver combinations of therapies selectively to cancer stem cells, bypassing the limitations of traditional treatments which often target single genes or redundant signalling pathways. Gene therapy is now a clinically validated technology that can be leveraged to overcome some of the drug delivery challenges encountered by past drug candidates, and I look forward to translating the full potential of Cellinta’s platform.”

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Issue Number: PN2009

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