< PreviousM&A ROUND-UP 10 Pharma Business International www.pbiforum.net © Shutterstock /Sundry Photography A flurry of activity 10-13.qxp_Layout 1 07/12/2020 10:50 Page 1Pharma Business International 11 www.pbiforum.net M&A ROUND-UP Back in September, Gilead Sciences announced that it was strengthening and diversifying its oncology offering with the acquisition of New Jersey-based biotech company, Immunomedics. The deal, valuing the latter at $21 billion, provides Gilead with Trodelvy (sacituzumab govitecan-hziy), a first-in-class Trop-2 directed antibody- drug conjugate (ADC) that was granted accelerated approval by FDA in April for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. The deal completed in early November with Immunomedics becoming a wholly- owned subsidiary of Gilead. At the time, Daniel O’Day, Chairman and CEO of Gilead Sciences, said: “We are very pleased to reach today’s milestone and to welcome the talented Immunomedics team to the Gilead family. There is a lot of important work ahead of us to deliver on the vast potential that Trodelvy offers for patients with cancer. Together we will bring Trodelvy to many more patients around the world with triple-negative breast cancer and continue to explore its potential in many other types of cancer, both as a monotherapy and in combination with other treatments.” November also saw the completion of Bristol Myers Squibb’s (BMS) $13.1 billion acquisition of MyoKardia, a precision medicine specialist based in Brisbane, California. The deal sees BMS gain mavacamten, a potential first-in- © Shutterstock /nitpicker 12 Á Ordinarily, in the last M&D round-up of the year, Pharma Business International looks back at the biggest deals of the year. However, with a spate of major acquisitions over the last few months, this issue will focus on 2020’s last quarter. 10-13.qxp_Layout 1 07/12/2020 10:50 Page 2© Shutterstock /nitpicker M&A ROUND-UP 12 Pharma Business International www.pbiforum.net class cardiovascular medicine for the treatment of obstructive hypertrophic cardiomyopathy (HCM), a chronic heart disease with high morbidity and patient impact. A New Drug Application for mavacamten for the treatment of symptomatic obstructive HCM – based on data from the EXPLORER-HCM study – is expected to be submitted to the US FDA in the first quarter of 2021. “The MyoKardia team has revolutionized cardiovascular treatments to address significant unmet medical needs, and we look forward to helping more patients together,” said BMS Board Chair and CEO, Giovanni Caforio at the time of the closure. “With MyoKardia, we are bolstering our leading cardiovascular franchise and adding exceptional scientific capabilities, a potentially transformative new medicine with significant commercial potential and a promising pipeline of candidates. Cardiovascular remains an important therapeutic area for Bristol Myers Squibb with a strong legacy and a promising future.” In a third multi-billion deal that moved to completion in November was Bayer’s purchase of North Carolina’s Asklepios BioPharmaceutical (AskBio) for up to $4 billion. The deal, for up to $4 billion, sees Bayer broaden its cell and gene therapy innovation base. AskBio’s development portfolio includes investigational pre- clinical and clinical stage candidates for the treatment of neuromuscular, central nervous system, cardiovascular and metabolic diseases. Bayer will own full rights to AskBio’s gene therapy platform, including a broad intellectual property portfolio and an established contract development and manufacturing organisation (CDMO) laying the foundation for future partnerships in the area of adeno- associated virus (AAV) therapies. The addition of AskBio to Bayer’s emerging cell and gene therapy (CGT) business strengthens Bayer’s commitment to the field. It complements the 2019 acquisition of BlueRock Therapeutics and consolidates Bayer’s ambition to create platforms with the potential to have an impact in multiple therapeutic areas. Bayer will pay an upfront consideration of $2 billion and potential success-based milestone payments of up to $2 billion. Some seventy-five per cent of the potential success-based milestone payments are expected to be due during the course of the next five years and the remaining amount late thereafter. “With this acquisition, Bayer significantly advances the establishment 10-13.qxp_Layout 1 07/12/2020 10:50 Page 3© Shutterstock /Atmosphere1 Pharma Business International 13 www.pbiforum.net M&A ROUND-UP of a cell and gene therapy platform that can be at the forefront of breakthrough science, contributing to preventing or even curing diseases caused by gene defects and further driving company growth in the future,” said Werner Baumann, Chairman of the Board of Management (CEO) of Bayer. As of writing, the deal has yet to close, but is expected some time in the fourth quarter of this year. November also saw Merck bolster its oncology pipeline with the announcement that it was acquiring San Diego biopharma company, VelosBio, for $2.75 billion. VelosBio is committed to developing first-in-class cancer therapies targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1). Its lead investigational candidate is VLS-101, an antibody-drug conjugate (ADC) targeting ROR1 that is currently being evaluated in a Phase 1 and a Phase 2 clinical trial for the treatment of patients with hematologic malignancies and solid tumours, respectively. This isn’t the only deal Merck has announced in the last few months. The company, looking to bolster its suit of clinical programmes targeting COVID-19, has acquired OncoImmune for $425 million. OncoImmune recently announced positive top-line findings from an interim efficacy analysis of a Phase 3 study evaluating its lead therapeutic candidate CD24Fc for the treatment of patients with severe and critical COVID-19. Interim analysis of data from 203 participants (seventy-five per cent of the planned enrolment) reported by OncoImmune indicated that patients with severe or critical COVID-19 treated with a single dose of CD24Fc showed a sixty per cent higher probability of improvement in clinical status, as defined by the protocol, compared to placebo. The risk of death or respiratory failure was reduced by more than fifty per cent. As per the agreement, prior to the completion of the acquisition, OncoImmune will spin-out certain rights and assets unrelated to the CD24Fc program to a new entity to be owned by the existing shareholders of OncoImmune. In connection with the closing of the acquisition, Merck will invest $50 million, and become a minority shareholder, in the new entity. Both Merck deals are slated to close before the end of 2020. Be sure to join us for our first issue of 2021 where – new multi-billion-dollar deals aside – we’ll be looking back at the biggest deals of 2020. 10-13.qxp_Layout 1 07/12/2020 10:50 Page 4ASTHMA EXPOSÉ 14 Pharma Business International www.pbiforum.net According to the Centres for Disease Control and Prevention (CDC), 1 in 13 people suffer from Asthma, which equates to over 25 million Americans. The figures are no better in the UK with 5.4 million adults and 1.1 million children (1 in 12) suffering. As of yet, there is no cure for asthma, leaving pharmaceutical companies to work instead on managing and preventing deadly asthma attacks. Its widespread prevalence across all countries of the world makes it a lucrative market, and one that isn’t likely to go anywhere with no cure in sight. Severe asthma Of those with asthma, approximately ten per cent suffer from what is known as severe asthma. Despite the use of inhaled asthma controller medicine, currently available biologic therapies and OCS, many severe asthma patients remain uncontrolled. Due to the complexity of severe asthma, many patients have unclear or multiple drivers of inflammation and may not qualify for or respond well to a current biologic medicine. Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life There is news on the horizon for those with severe asthma, however. AstraZeneca and Amgen recently announced positive results from the NAVIGATOR Phase III trial for the potential new medicine tezepelumab in patients with severe, uncontrolled asthma. NAVIGATOR met the primary endpoint with tezepelumab added to standard of care (SoC) demonstrating a statistically significant and clinically meaningful reduction in the Breathing easy In a time of COVID, it can be easy to forget about other widespread killers. One we have all grown used to living with is asthma, and while a vaccine or cure for that may not be on the horizon, research is still being conducted into managing the condition. 16 Á 14-17.qxp_Layout 1 07/12/2020 10:50 Page 1Pharma Business International 15 www.pbiforum.net ASTHMA EXPOSÉ © Shutterstock /Antonio Guillem 14-17.qxp_Layout 1 07/12/2020 10:50 Page 2ASTHMA EXPOSÉ 16 Pharma Business International www.pbiforum.net annualised asthma exacerbation rate (AAER) over fifty-two weeks in the overall patient population, compared to placebo when added to SoC. SoC was medium- or high-dose inhaled corticosteroids (ICS) plus at least one additional controller medication with or without oral corticosteroids (OCS). In the subgroup of patients with baseline eosinophil counts less than 300 cells per microlitre the trial also met the primary endpoint, with tezepelumab demonstrating a statistically significant and clinically meaningful reduction in AAER. Similar reductions in AAER were observed in the subgroup of patients with baseline eosinophil counts less than 150 cells per microlitre. Tezepelumab was very well tolerated in patients with severe asthma. Preliminary analyses show no clinically meaningful differences in safety results between the tezepelumab and placebo groups. Allergic asthma Research is being conducted into ways to manage asthma attacks brought on by allergic reactions – which is known to be the most common form of asthma, caused when foreign substances enter the airways and cause an allergic reaction. It’s already known that the body has natural defences against foreign substances in the form of phlegm and other respiratory cells, but doctors now believe it might be possible to program epithelial cells (responsible for regulation of mucus production) to respond more rapidly to foreign allergens. At the moment, researchers have isolated the cells responsible using gene sequencing and molecular imaging and identified the RNAs that are responsible for immune reactions. This may pave the way for future studies into manipulating those, however, essentially allowing for those immune cells to be “trained” to respond more rapidly and efficiently to the invasion of foreign allergens. While this will by no means be a cure to the problem, it could mean a much lower rate of mortality for those suffering from allergic asthma, as well as an improved quality of life. Development taking place despite COVID Vectura Group, an industry leading inhalation CDMO, has announced that it has signed a global out licence and development agreement with Kinaset Therapeutics for the development and commercialisation of VR588, a preclinical novel inhaled pan-JAK inhibitor for the prevention and treatment of severe asthma. Pan-JAK inhibitors have been developed and tested in clinical trials, approved and commercialised for many different indications but mainly for the treatment of chronic inflammatory conditions associated with an overactive immune response. VR588 was previously developed by Vectura as part of its former speciality pharma pipeline. This agreement provides an opportunity for Vectura to realise value from its historical research and investment in VR588, whilst expanding its CDMO development services portfolio by supporting the product’s further development with Kinaset. Under the terms of the agreement, Kinaset’s lead development programme will be an inhaled product for severe asthma delivered through a dry powder device. Vectura will provide fee for service development expertise to Kinaset to formulate this product to support Phase I studies, and ultimately through to commercialisation. Vectura will grant a license to Kinaset to develop and commercialise VR588, in return for development and sales milestones, and future royalties. Kinaset may pursue VR588 products in other indications and Vectura would be entitled to milestones and royalties on future products. Will Downie, Chief Executive Officer of Vectura, commented: “We look forward to working closely with Kinaset to support their development of this product, with the potential to bring a new treatment option to asthma patients in the future. This agreement is in line with our CDMO strategy to leverage our deep expertise, built through years of research in inhaled drug development, to help customers bring new inhaled therapies to market.” 14-17.qxp_Layout 1 07/12/2020 10:50 Page 3Pharma Business International 17 www.pbiforum.net ASTHMA EXPOSÉ © Shutterstock /Nerthuz 14-17.qxp_Layout 1 07/12/2020 10:50 Page 4ANTIDEPRESSANTS 18 Pharma Business International www.pbiforum.net © Shutterstock / Lightspring 18-21.qxp_Layout 1 07/12/2020 10:51 Page 1Pharma Business International 19 www.pbiforum.net ANTIDEPRESSANTS What’s new in antidepressants? What’s new in antidepressants? An antidepressant used to cure COVID? Antidepressant fluvoxamine has recently been tested as a potential treatment for COVID-19 in the US. While the sample size was small (only a little over 150) the results saw that those confirmed to have coronavirus showed a reduce incident level of serious COVID-19 conditions after taking the drug. None of the patients taking fluvoxamine deteriorated, while several on placebo medicine had their conditions grow worse. While the study was conducted on patients with mild coronavirus and there is no suggestion it could be a cure, the research does suggest that the antidepressant may be useful in stopping milder cases of COVID-19 from getting worse. This is not actually the first case of an antidepressant being used to treat respiratory diseases. In 1950, the first antidepressant, iproniazide, was used to treat tuberculosis. The aforementioned small sample size may hold the study back from gaining too much weight, however, and given the advent of a vaccine for COVID-19, the discovery may also be found to have come too late. That said, given that people with certain conditions would be at higher risk of developing COVID even with a vaccine, there may Pharma Business International takes a look at the latest news in the antidepressants industry. 20 Á 18-21.qxp_Layout 1 07/12/2020 10:52 Page 2Next >