< PreviousM&A ROUND-UP 10 Pharma Business International www.pbiforum.net Shortly after Merck successfully closed the deal, Sanofi announced it had completed its $2.5 billion acquisition of Californian biotech, Synthorx. Less than two months after the deal was first announced, Synthorx has now become a wholly-owned subsidiary of Sanofi in a move that strengthens its growing position in the fields of oncology and immunology. Specifically, bringing Synthorx into the fold grants it access to THOR-707, an engineered not-alpha IL-2 for the treatment of solid tumours which induces strong immunological responses in vivo. According to Sanofi CEO Paul Hudson, the deal also provides it with access to “additional intriguing pre-clinical assets”. With Bristol-Myers Squibb having finally completed its $74 billion acquisition of Celgene last year, AbbVie’s ongoing acquisition of Ireland-headquartered Botox maker Allergan is the biggest industry deal still clearing regulatory hurdles. The $63 billion deal took a major step forward towards the end of January after Allergan agreed to divest brazikumab, an investigational IL-23 inhibitor being tested as a treatment for Crohn’s disease and ulcerative colitis, and Zenpep, a treatment for exocrine pancreatic insufficiency due to cystic fibrosis and other conditions, to comply with regulators. Brazikumab will be acquired by AstraZeneca, while Nestlé will acquire and take full operational ownership of Zenpep as well as acquiring Viokace, another pancreatic enzyme preparation, as part of the same transaction. The closings of each divestiture are contingent on approval from the US Federal Trade Commission and the European Commission. Both companies continue to expect a first quarter 2020 closing of the deal. With the divestitures taking place, there are still certain other customary closing conditions to be 08-11.qxp_Layout 1 10/02/2020 13:01 Page 3Pharma Business International 11 www.pbiforum.net M&A ROUND-UP © Shutterstock Susan Montgomery met, so we’ll see if that’s the case in next issue’s column. As of publishing, there’s only been one newly announced deal over the billion-dollar threshold. In mid-January, Eli Lilly announced it was expanding its immunology pipeline with the $1.1 billion acquisition of Dermira, a Californian biopharma developing therapies for chronic skin conditions. The all-cash acquisition adds lebrikizumab, a novel, investigational, monoclonal antibody designed to bind IL-13 with high affinity to Lilly’s pipeline. It is currently being evaluated in a Phase 3 clinical development programme for the treatment of moderate-to-severe atopic dermatitis in adolescent and adult patients ages twelve years and older. A vote of confidence came late last year after it was granted Fast Track designation by the US Food and Drug Administration (FDA). The deal will also expand Lilly’s portfolio of marketed dermatology medicines with the addition of Qbrexza (glycopyrronium) cloth, a medicated cloth approved by the FDA for the topical treatment of uncontrolled excessive underarm sweating. “The acquisition of Dermira is consistent with Lilly’s strategy to augment our own internal research by acquiring clinical phase assets in our core therapeutic areas and leveraging our development expertise and commercial infrastructure to bring new medicines to patients,” said Patrik Jonsson, Lilly Senior Vice President and President of Lilly Bio-Medicines. In the interim until our next issue, there’s a high chance that there’ll be more billion-dollar- plus deals taking place in the life sciences sector which you can trust we’ll explore in the next round-up. CORONAVIRUS 12 Pharma Business International www.pbiforum.net Focus on coronavirus As the World Health Organisation declares the novel coronavirus a global emergency, Pharma Business International takes a closer look at the outbreak and what researchers are doing to combat the virus. © Shutterstock /creativenekoPharma Business International 13 www.pbiforum.net CORONAVIRUS The first case of new coronavirus strain 2019-nCoV was reported in China in late December. By the end of January, it had been declared a public health emergency of international concern by the World Health Organization (WHO) as it continued to spread outside of China and amid concerns it could spread to countries with weaker health systems. The strain belongs to the same family of viruses that includes the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). As of publishing, the death toll has exceeded 900, with over 400,500 confirmed cases globally, more than doubling the death toll from the SARS epidemic that claimed 349 lives in 2003. The outbreak originated in Wuhan in Hubei province which, at eleven million people, is China’s fifth largest city. The source is believed to have originated in a wet market where wild animals – including bats and snakes – are traded illegally. Coronaviruses are known to jump from animals to humans. SARS, for example, was thought to have evolved from bats to civet cats to humans in China, while MERS evolved from bats to camels in the Middle East. An initial analysis of 2019-nCoV suggested it was similar to coronavirus seen in snakes, but a detailed paper showed that the genetic make-up of this new strain is ninety- six per cent identical to that of coronavirus found in bats. The first people infected were thought to be predominantly comprised of stallholders from the wet market from contact with animals, but some early cases show infections among people who had no link to the market at all, indicating that the initial route of human infection may pre-date the market cases. As researchers try and determine the exact origins of the virus, the number of those infected continues to grow. The Centres for Disease Control and Prevention in the US says that most patients of this latest strain start with a fever, cough and shortness of breath with other common symptoms including muscle pain and fatigue. All confirmed cases had pneumonia and lung abnormalities on CT scans. The disease continues to spread with the first fatality outside of China occurring after a Chinese citizen died in the Philippines after travelling from Wuhan. Outside of China, Hong Kong and Macau, the highest confirmed cases are in Japan, Thailand, Singapore, South Korea, Australia and the US. Here in the UK, there are eight confirmed cases and the government has declared the virus a “serious and imminent threat” to public health and announced new measures allowing people to be forcibly quarantined in isolation facilities. The outbreak prompted an unprecedented response from Chinese authorities, with Wuhan cancelling all outbound busses, trains, flights and ferries in a major lockdown of the city. A further ten cities were also quarantined to minimise chances of the outbreak spreading. These restrictions are thought to affect fifty million people with residents unable to leave Wuhan without a “special reason”. Speaking to the Associated Press, Gauden Galea, the WHO’s China Representative, said: “To my knowledge, trying to contain a city of eleven million people is new to science. It has not been tried before as a public-health measure, so we cannot say at this stage if it will work or not.” However, Chinese top leadership has admitted to “shortcomings and deficiencies” in the country’s response to the outbreak. The quarantines were highly controversial both in and outside of China, especially as they coincided with Lunar New Year celebrations. Typically, the annual holiday fills up the country’s transport as three billion people travel home to be with family. However, the Chinese government asked people to cancel their plans to visit Wuhan, while Beijing’s government has cancelled its spring festival. It isn’t only China that is shutting down its borders and transportation, with the US denying entry to foreign nationals 14 ÁCORONAVIRUS 14 Pharma Business International www.pbiforum.net who have visited China in the last few weeks. Australia, meanwhile, is baring entry to non-citizens coming from China. Shortly before publishing, the nation’s finance ministry announced that all levels of government had allocated a total of $10.26 billion to combat the epidemic. These efforts serve to contain the outbreak and prevent, or slow down, the spread of infection. There are currently no existing therapeutics for this strain of coronavirus, although many of the symptoms can be treated with existing drugs – for example, AbbVie’s HIV drug Kaletra (which combines lopinavir and ritonavir) was selected by Chinese authorities for use against the pneumonia triggered by the virus. Part of the issue is that despite the massive impact that virus outbreaks can have – like the plunging of China’s stock market after reopening after the Lunar New Year – there isn’t any real business model in place to justify developing vaccines for emerging viral threats. The other major issue is the development timeframe of the treatments themselves. There are two ways to treat viral infections. The first is to find small molecules that stop viruses replicating by interfering with viral proteins. As ninety-nine per cent of potential small molecule drugs fail, developing new antivirals could take years. The second approach is to use antibodies, large proteins that bind to viruses and trigger their destruction. Although there was no quick coordinated response from pharma, there are many efforts and studies now in place rapidly find treatments. The Coalition for Epidemic Preparedness Innovations (CEPI) is funding three programmes to develop vaccines against 2019-nCoV into clinical testing as soon as possible. The aim is to fast-track a vaccine within six to eight months, something Chief Executive Dr Richard Hatchett described as “unprecedented”. The programmes will leverage rapid response platforms already supported by CEPI as well as a new partnership. To help support the development, the UK government has donated £20 million. Alongside these efforts from CEPI and academia, pharmaceutical firms are stepping up to the challenge. Johnson & Johnson has unveiled a multi-pronged approached, collaborating with global partners to make an effective vaccine, testing whether existing medicines could tackle the virus, and donating antiviral drugs to Chinese hospitals. Gilead has provided doses of an experimental antivirus drug to doctors for treating a small number of patients infected. The company has formalised an agreement with Chinese authorities to conduct a clinical trial of the experimental Ebola drug remdesivir in infected patients. The drug isn’t currently approved for use in humans by regulators anywhere in the world, unlike some of the other antivirals currently being examined. Roche says it has developed the first commercial test for the outbreak. According to the company, the diagnostic can detect the virus in a few hours. French non-profit, the Institut Pasteur, said it has sequenced the entire genome of the virus and its scientists have made virus samples available for research. One encouraging development comes from Thailand where, as of writing, there are nineteen confirmed cases of 2019- nCoV. Thai doctors have hailed a treatment combining Kaletra – AbbVie’s HIV drug – with Roche’s anti-flu medication stelmativir – sold as Tamiflu. Tamiflu was selected because of research that showed it helped patients with MERS. A study in France recommended it be used in MERS patients, but discontinued if tests showed that patients didn’t have the flu. Therefore, there isn’t enough evidence in place to support the effectiveness of this combination just yet, but Somkiat Lalitwongsa, Director of the Rajavithi Hospital in Bangkok, told reporters that “the result look good so far”. The number of those infected by 2019- nCoV continues to increase and the death toll is rising as the global emergency continues to spread. However, with an unprecedented response in place to find vaccines as quickly as possible, the outbreak may yet be short lived. 12-15.qxp_Layout 1 10/02/2020 13:02 Page 3Pharma Business International 15 www.pbiforum.net CORONAVIRUS © Shutterstock /leungchopanQ&A - FUTURE OF HEALTHCARE 16 Pharma Business International www.pbiforum.net © JM Huron for Novadiscovery Novadiscovery’s aim is to reduce R&D costs and time-to-market of novel drugs. Will this approach disrupt the industry standard? François-Henri Boissel: Our approach offers a solid solution to develop drugs more efficiently. In a specific case of drug repositioning in cardiotherapy, our platform helped reduce time-to-market by a year. We believe that in silico clinical trials will become the third pillar of drug R&D, as a complementary approach to in vivo and in vitro explorations. It is about improving productivity and innovation potential. It is not a disruption so much as a natural evolution of the R&D paradigm - it needs to remain grounded in rigorous clinical development methodology. Tanja Dowe: By moving from “one pill fits all” to personalised, targeted, precision medicine, we have already disrupted the industry standard. The old way of developing drugs simply does not work with that. It is too slow and too expensive. On the other hand, we have a huge societal issue with the cost of healthcare. We have to make healthcare more affordable and more accessible. As a pharmaceutical company, we can answer that challenge by disrupting the way we develop drugs – bringing better outcomes to patients and reducing the time and cost of development by smart data technologies. Novadiscovery is on that path with its in silico trial platform. In silico trials are virtual trials run on computer using complex algorithms. By investing in Novadiscovery, Debiopharm is bringing one piece of the puzzle to the table, and saying “yes, we can disrupt the way we develop drugs”. Novadiscovery has recently closed the first tranche of a multi-million-euro Series A funding round with Debiopharm Innovation Fund. How will this funding be used to advance the company’s technology and reach? François-Henri Boissel: We will use this funding to accelerate Jinko’s development roadmap and make it available to a global customer base. We will expand our footprint in the US market, and plan to start the deployment of a salesforce in the Boston area in a couple of months. How will the Fund continue to support Novadiscovery in the months and years to come? Tanja Dowe: Our support to start-ups goes far beyond financing. We mentor the companies and guide them to achieve their ambitions. In practice, we offer our development experts to be a sounding board for Novadiscovery, for understanding the customer pain. We provide Novadiscovery with a customer perspective in order to help package their offering in a way that is easy to adopt by pharmaceutical companies. And we will explore with Novadiscovery Q&A We spoke with François-Henri Boissel, CEO of French biotechnology company Novadiscovery, and Tanja Dowe, CEO of Debiopharm Innovation Fund, about advances in drug discovery, clinical trials and what the future holds for healthcare. François-Henri Boissel, CEO of French biotechnology company NovadiscoveryPharma Business International 17 www.pbiforum.net Q&A - FUTURE OF HEALTHCARE new value-added development avenues for the future. Can you tell us more about Novadiscovery’s in silico clinical trial simulation platform, Jinko? François-Henri Boissel: Our platform, Jinko, brings together the most advanced technology and expertise on the market. Jinko is an integrated solution spanning the entire clinical trial simulation workflow: biological knowledge manager, disease model design, in silico experiments execution (scenario testing) and results analysis. The platform can be deployed in any disease area and is usable from early research down to late-stage clinical development. Ten clients already use our services, including two major pharmaceutical companies. Artificial intelligence is being utilised in a number of exciting ways across the pharmaceutical industry. How is it being used for the Jinko platform? François-Henri Boissel: Some of our modules leverage AI, such as the one designed to calibrate our disease models. Tanja Dowe: Today healthcare is moving towards an era of integrated knowledge. AI-only platforms are not the solution: we need integrative platforms like what Novadiscovery offers, bringing both digital technologies, including AI, and the best medical expertise. What makes Novadiscovery’s model so solid – and different from other competitors on the market – is that their expertise comes originally from clinical trial development. They are biologists at the core. They know how to collect the relevant data and get legitimate and robust analyses. How will patients benefit from advancing this platform? François-Henri Boissel: Running in silico trials allows us to identify the optimal responders within a patient population. For this reason, when we reach the in vivo phase of a trial, the patients enrolled are likelier to respond to the therapy. “Real-world” patients will also benefit from improved outcomes through more personalised treatment options. Tanja Dowe: With this platform, the whole R&D process is faster and more efficient. It will help bring to market the right drugs, for the right patients, in a faster way. From an affordability perspective, making drug development more efficient will have an impact on costs, making drugs more accessible to patients. The pharmaceutical and healthcare industries have been increasingly adopting smart data and digital health solutions since Debiopharm Innovation Fund was founded in 2008. What technologies will have the greatest impact in the years to come? Tanja Dowe: Today the mainstream of healthcare is in the era of digital workflow solutions – tomorrow is for the real convergence of AI, medical understanding and true passion for solving problems for patients. AI is a technology that will unlock a lot of potential. But it cannot work alone. We need to combine it efficiently with biological and medical sciences. We need to think digital twins, predictive digital biomarkers, personalised therapy and digital patient monitoring as a package. These all combined will lead to the biggest value opportunity: better patient outcomes, better quality of life. On the pharmaceutical industry side, model informed drug development, real world control arms, and digital therapeutics and companions will change the way we develop and deliver drugs. What’s your long-term vision of healthcare? Tanja Dowe: We need to deliver health in a bigger sense, not just a pill. The interface between pharma, IT, medtech, and consumer health will blur. New types of collaborations and a mixture of technologies are required to meet patients’ need. Today, pharmaceutical companies and healthcare providers are piloting predictive, adaptive, patient centric and data driven solutions, but we are not yet utilising them fully. This will come. Where will that lead us? It is like in the 1990’s, thinking that email was an incredible highlight of electronic communication. We just could not imagine where all the technology development would lead us. Tanja Dowe, CEO of Debiopharm Innovation Fund 16-17.qxp_Layout 1 10/02/2020 13:03 Page 2ANTIBIOTICS EXPOSÉ 18 Pharma Business International www.pbiforum.net 18-21.qxp_Layout 1 10/02/2020 13:04 Page 1Pharma Business International 19 www.pbiforum.net ANTIBIOTICS EXPOSÉ © Shutterstock /Christoph Burgstedt While concerns over antimicrobial resistance (AMR) continue to mount, insufficient private investment, alongside a lack of innovation in antibiotic development, as highlighted by the World Health Organisation (WHO), are only furthering the growth of drug resistant infections. While fifty antibiotics are in development, they are set to bring minimal benefit over existing treatments and few target critical resistant bacteria, Gram-negative bacteria. WHO has stressed the need for the pharmaceutical industry and countries to “step up” and contribute to the immediate threat of AMR with sustainable funding and innovative new medicines. In the US alone 35,000 people die a year as a result of an antibiotic-resistant infection, while in Europe the number sits at approximately 33,000. Public Health England’s (PHE) latest English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) shows how AMR is rapidly developing with an estimated 61,000 antibiotic resistant infections reported in England in 2018, rising nine per cent from 2017. Today, routine surgeries, transplants, chemotherapy, and other procedures cannot be performed without risking serious infections due to poor access to effective antibacterial treatments. Despite the fact that AMR has been named a global health emergency by the UN, large pharma companies are exiting the antibiotic field, and it is SMEs driving research and development. Getting antibiotics to market is challenging and holds a high failure rate. It can take fifteen years and more than $1 billion to develop a new antibiotic. In addition, with the antibiotic field surrounding drugs that need to be used as little as possible to prevent resistance, plus the fact that antibiotics comparatively hold a lower price to other drugs, incentives to develop them are stunted. Though there is sustained investment in early R&D and diagnostics in AMR, with an encouraging bio- tech pre-clinical pipeline, the funding available for costly late stage research is particularly insufficient, which could see promising early stage compounds never reach patients, as a report from the AMR Industry Alliance - formed of drug companies and industry associations - highlighted at the start of 2020. The alliance says that governments must put in place new mechanisms and incentives for antibiotic development, compensate for funding shortfalls and members are “eager to find partners in piloting new reimbursement mechanisms and incentives that improve patient access and enable sustainable private investment in the development of new tools to tackle AMR.” While a current lack of incentives and failing payment models are plaguing the field, some steps Reacting to resistance With the threat of antimicrobial resistance only growing, funding, incentives, overprescribing and diagnostic tests are all topics on the tongue of the antibiotics field. 20 ÁNext >