< PreviousM&A ROUND-UP 10 Pharma Business International www.pbiforum.net “This transaction brings together Nestlé’s nutritional science leadership with one of the most innovative companies in food allergy treatment,” said Nestlé Health Science CEO Greg Behar. “Together we will be able to offer a wide range of solutions that can transform the lives of people suffering from food allergies around the world.” NHSc currently has a total investment in Aimmune of $473 million, an approximate 25.6 per cent equity ownership stake. It made its initial investment of $145 million in Aimmune in November 2016, followed by further investments of $30 million in February 2018, $98 million in November 2018 and $200 million in January 2020. As per this latest agreement, Nestlé’s wholly- owned subsidiary, Société des Produits Nestlé, will commence a cash tender offer to acquire all outstanding shares of Aimmune common stock that are not already owned by NHSc for $34.50 per share in cash, including the shares of Aimmune held by NHSc, of approximately $2.6 billion. Lastly for the billion-dollar bracket this issue sees Merck take a $1 billion stake in Washington-based biotech Seattle Genetics as part of two new strategic oncology collaborations between the two companies. The companies will globally develop and commercialise Seattle Genetics’ ladiratuzumab vedotin, an investigational antibody-drug conjugate (ADC) targeting LIV-1 currently in phase 2 clinical trials for breast cancer and other solid tumours. The collaboration will pursue a broad joint development program evaluating ladiratuzumab vedotin as monotherapy and in combination with Merck’s anti- PD-1 therapy Keytruda (pembrolizumab) in triple-negative breast cancer, hormone receptor-positive breast cancer and other LIV- 1-expressing solid tumours. Seattle Genetics will receive a $600 million upfront payment and Merck will make a $1.0 billion equity investment in 5.0 million shares of Seattle Genetics common stock at a price of $200 per share. In addition, the company is eligible for progress-dependent milestone payments of up to $2.6 billion. Separately, Seattle Genetics has granted Merck an exclusive license to commercialise Tukysa (tucatinib), a small molecule tyrosine kinase inhibitor, for the treatment of HER2-positive cancers, in Asia, the Middle East and Latin America and other regions outside of the US, Canada and Europe. Seattle Genetics will receive $125 million from Merck as an upfront payment and is eligible for progress-dependent milestones of up to $65 million. Under the billion-dollar bracket, we see Takeda continuing its strategy of divesting non-core profits as part of its ongoing portfolio simplification and optimisation. In September, the company divested a portfolio of select non-core prescription pharmaceutical products sold predominantly in Europe and Canada to Cheplapharm, a specialty Germany pharmaceutical company, for $562 million. The portfolio, which generated FY 2019 net sales of approximately $260 million, includes cardiovascular/metabolic and anti-inflammatory products along with calcium. Finally, San Diego biopharma Ligand Pharmaceuticals is acquiring Pfenex, a biotech based in California, in a deal worth up to $516 million. The acquisition will provide Ligand with access to a proprietary, protein expression technology that is utilised in various commercial and development- stage biopharmaceutical programs. It will also provide numerous major collaborations with major pharma players for treatments and vaccines – including Merck, Jazz Pharmaceuticals, Serum Institute of India and Alvogen. Moreover, the deal gives Legand a state-of-the-art process development operation located in San Diego with scalable equipment and engineering capabilities designed to serve the world’s largest pharmaceutical companies. 08-11.qxp_Layout 1 12/10/2020 10:59 Page 3Pharma Business International 11 www.pbiforum.net M&A ROUND-UP © Shutterstock /T ada Images 08-11.qxp_Layout 1 12/10/2020 10:59 Page 4PRECISION MEDICINE EXPOSÉ 12 Pharma Business International www.pbiforum.net treatments Pharma Business International delves into recent strides for precision medicine, highlighting studies that are expanding access to the approach, and displaying its potential. Tailoring 12-15.qxp_Layout 1 12/10/2020 11:00 Page 1Pharma Business International 13 www.pbiforum.net PRECISION MEDICINE EXPOSÉ With precision medicine, treatments are tailored to the individual characteristics of a patient, considering genes, environment, and lifestyle. The aim is to match the right treatment with the right patient, delivering the correct dose, at the right time, using therapies that take into account all that makes a patient different from another with a similar diagnosis, to improve outcomes. Though targeted therapies often come with a high cost, precision medicine allows clinicians to customise treatments and prevention strategies, predict which are likely to work with which people, to bypass and reduce costs associated with trying out ineffective therapies for patients and health systems. Precision medicine has primarily impacted oncology, with advances in genomics and the mechanisms of targeted therapies pushing this area forwards. More studies are getting underway to advance precision medicine and its reach. A recent step forward has seen more focus placed on rare cancers, which have historically received less financial support than common tumour applications. TargetCancer Foundation, with Foundation Medicine, investigators from academic institutions, and support from Bayer, have enrolled the first patients in the TCF-001 TRACK study. The study is looking to provide individualised treatment recommendations to patients who have rare cancers and utilises genomic analysis and consultation with rare cancer clinicians and researchers. A molecular tumour board will share recommendations with healthcare providers and patients to provide the most expansive variety of options. Treatments and responses will be tracked for a year, observing outcomes based on molecularly informed treatment decisions. With genomic testing, DNA alterations can be identified, as well as changes, in cancer cells that dictate how a tumour behaves. Genomic testing 14 Á © Shutterstock /LeoW olfert 12-15.qxp_Layout 1 12/10/2020 11:00 Page 2PRECISION MEDICINE EXPOSÉ 14 Pharma Business International www.pbiforum.net results may assist healthcare providers when matching patients to approved and investigational therapies as a result of the specific alteration identified. Further ahead in displaying the potential of precision medicine, a recent boon came as a study revealed patients receiving care for advanced cancer at Moores Cancer Centre were more likely to survive or see a longer period without disease progression if receiving personalised cancer therapy. A multidisciplinary molecular tumour board was formed to advise physicians on care using a patient’s molecular tumour makeup to create precision medicine strategies. Those who received a therapy recommended by the board were better matched to genomic alterations in their cancer and had improved outcomes. The three-year survival for patients with the highest degree of matching and who received a personalised cancer therapy was approximately fifty-five per cent, next to twenty-five per cent in patients who received therapy that was unmatched or had low degrees of matching. Utilising next-generation sequencing, novel potential targets for patients can be identified to improve outcomes. However there are challenges to using this approach, said Shumei Kato, MD, associate professor of medicine at UC San Diego School of Medicine, Moores Cancer Centre medical oncologist, and first author. “One of the hurdles is that every cancer patient appears to be carrying different molecular and genomic patterns despite having the same cancer type. This can be challenging since we are customising therapy based on the unique genomic pattern patients have, and thus it is difficult to predict the response. In addition, this approach requires multidisciplinary expertise as well as access to drugs or clinical trials not always available in smaller practices.” Meanwhile progress is being made to accelerate access to precision medicine for breast cancer patients. Early results of a major clinical trial have revealed a blood test that can identify a variety of mutations in advanced breast cancer, tracking the disease as it evolves, can match women to effective targeted treatments. The Institute of Cancer Research (ICR), London, and The Royal Marsden NHS Foundation Trust, analysed blood samples from over 1,000 women to see if the blood test could help improve treatment for those whose breast cancer is caused by rarer mutations. Researchers detected mutations found in tumour DNA that had been shed into the bloodstream of women with advanced breast cancer, then matched patients to targeted treatments according to the mutations in the tumour DNA. Looking at three targetable defects in genes which drive breast cancer (HER2, AKT1 and ESR1), 142 women were given experimental drugs targeted against the specific characteristics of their cancer. Women with ESR1 mutations were treated with fulvestrant, while women with HER2 mutations received neratinib on its own or with fulvestrant. Women with AKT1 mutations were split into two groups, according to whether their cancer was 12-15.qxp_Layout 1 12/10/2020 11:00 Page 3Pharma Business International 15 www.pbiforum.net PRECISION MEDICINE EXPOSÉ oestrogen receptor positive, and treated with capivasertib plus fulvestrant, or with capivasertib alone. Some women with HER2 and AKT1 mutations responded to their treatments, suggesting liquid biopsies can successfully match patients with certain rare forms of advanced breast cancer to more effective treatments. Five out of twenty women with rare HER2 mutations matched to neratinib saw a beneficial response, and four out of eighteen patients with AKT1 mutations responded to capivasertib. However, the treatment targeting the ESR1 mutation was not effective. Researchers also validated the findings by checking tissue samples from the patients to confirm that the liquid biopsies had correctly identified the presence or absence of the mutations in over ninety-three per cent of cases. The team highlights that the plasmaMATCH trial’s findings will make a case for the adoption of liquid biopsies into clinical practice for patients with advanced cancer and help accelerate women’s access to the best precision medicines. This is reinforced by the fact that liquid biopsies are easier to take, quicker to analyse, and less painful than standard tissue biopsies. Various precision drugs are advancing through trials with exciting results. A major phase III clinical trial showed precision drug ipatasertib alongside current standard of care abiraterone, allowed some men with prostate cancer to live longer before their cancer worsened in comparison to those on abiraterone alone. The combination stopped the growth of a group of cancers lacking a functioning PTEN gene - involved in controlling cell growth which is faulty or absent in many prostate cancers. Cancers that lack the PTEN protein frequently come to rely on a strong driver of growth called AKT and are typically more aggressive. The ICR, London, and The Royal Marsden NHS Foundation Trust assessed the efficacy and safety of ipatasertib with abiraterone in men with advanced prostate cancer who had received no prior treatment. Out of 1,101 men, 521 lacked a fully functioning PTEN gene. Each patient was given steroids as well as abiraterone and ipatasertib or abiraterone and a placebo. The researchers found ipatasertib plus abiraterone as a first-line treatment enabled men with prostate cancer whose tumours lacked a functioning PTEN gene to live longer before their disease progressed, compared with abiraterone alone. Risk of tumour progression was reduced by twenty-three per cent in men treated with ipatasertib plus abiraterone, next to those just on abiraterone. The ipatasertib combination achieved a three- fold increase in complete remissions and around a twenty per cent increase in partial remissions in this aggressive type of prostate cancer. Johann de Bono, Professor of Experimental Cancer Medicine at the ICR and Consultant Medical Oncologist at The Royal Marsden, said: “PTEN is one of the most commonly deleted genes in prostate cancer, and as a result men often have a particularly poor prognosis, so it is great news that this study could open up a new precision medicine approach for these patients.” © Shutterstock /MIKHAIL GRACHIKOV 12-15.qxp_Layout 1 12/10/2020 11:00 Page 4STEM CELL THERAPIES 16 Pharma Business International www.pbiforum.net Stem cell therapies represent one of the most exciting and cutting-edge medical research avenues. Under the right conditions, be that in the body itself or in a laboratory environment, stem cells divide to form more cells called ‘daughter cells’ which either then become new stem cells in a process called self-renewal, or they become specialised cells – known as differentiation – with a more specific function such as blood, brain, heart muscle or bone cells. As no other cell in the body has the natural body to generate new cell types, stem cell therapies are uniquely positioned to enable scientists to tackle some of the most pressing and fatal diseases. And, as the Mayo Clinic points out, this means stem cells can increase the understanding of how diseases occur; generate healthy cells to replace diseases cells, and test new drugs for safety and effectiveness. The market is understandably growing and, according to the latest figures, is expected to reach $17.9 billion by 2027. As the market has expanded, it has yielded several breakthroughs and key developments, especially over the last few years. Stem cells have thus far shown to be a potential asthma treatment, as well as potentially improving cardiovascular disease treatment and, of course, being used against cancer. However, this year scientific focus has largely been aimed at SARS-CoV-2, the virus that causes COVID-19. As the first global pandemic in a century, the coronavirus crisis has provided a new benchmark for future pandemics. Therefore, approaches explored now are not only aimed at the current crisis, but will also have future pandemics factored in. In this way, stem cell therapies will become an important tool in our arsenal against pandemics here in the present, but also in the years and decades to come. The research breakthroughs that companies make now will inform our response to the next pandemic. Avacta Group, a UK-based biotech, has expanded its collaboration and license Therapies for the future The cutting-edge stem cell therapy market continues to grow as the pandemic intensifies; now scientists are taking aim at coronavirus and, in so doing, bolstering our response to future pandemics. 18 Á 16-19.qxp_Layout 1 12/10/2020 12:17 Page 1Pharma Business International 17 www.pbiforum.net STEM CELL THERAPIES © Shutterstock /HUANSHENG XU 16-19.qxp_Layout 1 12/10/2020 12:17 Page 2STEM CELL THERAPIES 18 Pharma Business International www.pbiforum.net agreement with Daewoong Pharmaceutical and AffyXell Therapeutics to develop stem cell treatments incorporating Avacta’s neutralising Affimer therapy for the treatment of seriously ill patients with COVID-19 and to also prepare to rapidly develop similar therapies for future global pandemics. Respiratory diseases such as COVID- 19 can cause serious damage to the lungs as a consequence of over- activation of the patient’s immune system, resulting in cytokine release syndrome that can potentially lead to multiple organ failure and death. Stem cell therapies offer a promising approach to repair the damage to lung tissues in these pulmonary diseases by controlling the immune balance. AffyXell Therapeutics, the next- generation cell and gene therapy joint venture between Avacta and Daewoong Pharmaceutical, is developing a novel class of mesenchymal stem cell (MSC) treatments that are engineered to also produce Affimer therapies in the patient at the site of action. The expansion of the agreement between Avacta, Daewoong Pharmaceutical and AffyXell extends the scope of the partnership to include Affimer molecules that target viruses, such as coronaviruses, in order to develop therapies that repair the lung damage caused by COVID-19 whilst also producing neutralising Affimer molecules to prevent the progression of the disease. AffyXell will engineer mesenchymal stem cells to express SARS-COV-2 neutralising Affimer molecules in order to develop treatments for seriously ill COVID-19 patients, and will also prepare for rapid development of next-generation stem cell therapies for future infectious respiratory disease outbreaks. “I am very pleased to have extended our collaboration and license agreement with Daewoong Pharmaceutical to include the SARS-COV-2 neutralising Affimer molecules for the treatment of COVID-19 and to create the potential to respond very rapidly in future to global virus threats,” said Dr Alastair Smith, Chief Executive of Avacta Group. “AffyXell will address the need over the coming years for advanced stem cell therapies to treat lung damage caused by cytokine release syndrome suffered by COVID-19 patients and, at the same time, help prevent disease progression in these patients through the action of a neutralising Affimer therapy. “More broadly, one of the key areas of unmet clinical need that AffyXell can address with its next-generation mesenchymal stem cell therapies is acute pulmonary diseases such as COPD and acute respiratory distress syndrome. We, and our partners in South Korea, are very excited by the potential to develop life improving treatments for patients with these serious respiratory diseases as well as COVID-19.” Seng-ho Jeon, CEO of Daewoong Pharmaceutical and AffyXell Therapeutics, said: “It is very encouraging that AffyXell now has the opportunity to expand the application of its next-generation stem cell platform technology to target viruses. The SARS- COV-2 neutralising Affimer to be developed in combination with AffyXell’s cell and gene technology is expected to be an innovative solution for COVID-19 patients suffering cytokine release syndrome. Daewoong has been also conducting several research programs and clinical trial for COVID-19. As the COVID-19 crisis has caused great difficulties worldwide, we will continue to focus our efforts to develop a novel therapeutic agent for COVID-19.” Although stem cell therapies are still very much in their infancy, they are rapidly emerging as one of the most promising therapeutic approaches not only to the coronavirus crisis, but to a myriad of the world’s most pressing diseases. In so doing, we will be better positioned for future outbreaks. If there’s a silver lining to the current pandemic, then being better prepared and defended in the years to come is certainly it. 16-19.qxp_Layout 1 12/10/2020 12:17 Page 3Pharma Business International 19 www.pbiforum.net STEM CELL THERAPIES © Shutterstock /Elena Pavlovich 16-19.qxp_Layout 1 12/10/2020 12:17 Page 4Next >