Your guide to the pharmaceutical world Volume 12 Issue 3 M&A round-up Deals in demand Warehousing and distribution Making the most of a warehouse Cleaning and maintenance Regular and often M&A round-up Deals in demand Warehousing and distribution Making the most of a warehouse Cleaning and maintenance Regular and often www.pbiforum.net8 12 16 24 Steve Fisher (s.fisher@blmgroup.co.uk) Michael Fisher (m.fisher@blmgroup.co.uk) Tess Egginton (t.egginton@blmgroup.co.uk) Angie Cooper (a.cooper@blmgroup.co.uk) Vicky Hunt (v.hunt@blmgroup.co.uk) Tel: +44 (0) 1472 310302 Angela Sharman (a.sharman@blmgroup.co.uk) Gary Jorgensen, Mark Casson, (studio@blmgroup.co.uk) Tel: +44 (0) 1472 310305, Fax: +44 (0) 1472 310317 Armstrong House, Armstrong Street, Grimsby, North East Lincolnshire DN31 2QE England All rights reserved. No part of this publication may be reproduced, transmitted, photocopied, recorded or otherwise without express permission of the copyright holder, for which application should be addressed first to the publisher. While every reasonable care is taken, neither the publisher nor its participating agents accept liability for loss or damage to prints, colour transparencies, negatives or other material of whatever nature submitted to this publication. The views expressed in this publication are not necessarily the views of those held by the publisher. News4 Stay up to date with the latest industry updates from the global pharmaceutical technology industry. M&A round-up8 Despite challenges, the pharma industry has kept its renewed interest in acquisitions. Process, control and automation12 Automation often focuses on manufacturing efficiency, but there are processes in pharmaceutical manufacturing where it is closer to a necessity. Training and skills development16 Pharma firms are struggling to find recruits with the right degrees and specialisations, and the problem shows no signs of going away. Flow measurement and control20 Ensuring product integrity, quality, and efficiency in the pharmaceutical industry relies on accurate flow measurement and control. We explore how precise monitoring and regulation help to enhance safety, compliance, and long- term business success. Warehousing and distribution24 The supply chain is being stretched, which means it’s up to warehousing and distribution centres to adapt to the demands and find a solution. But with space at a premium and construction not keeping up with demand, many companies are looking on how to get more from what they already have. Cleaning and maintenance28 Maintenance and cleaning of pharmaceutical manufacturing equipment is obviously important on the issue of hygiene and consumer safety, but adhering to the bare minimum to meet these quotas could be costing factories when it comes to efficiency and machine longevity. Events 32 We give a rundown of pharma events happening around the world. @pbiforum www.pbiforum.net company/pbiforum Cover photo courtesy: stock.adobe.com/StockPhotoPro4 Pharma Business International www.pbiforum.net Latest news WHO prequalifies new dengue vaccine A new vaccine for dengue has received prequalification from the World Health Organization (WHO). TAK-003 is the second dengue vaccine to be prequalified by WHO. Developed by Takeda, it is a live-attenuated vaccine containing weakened versions of the four serotypes of the virus that cause dengue. WHO recommends the use of TAK-003 in children aged 6–16 years in settings with high dengue burden and transmission intensity. The vaccine should be administered in a 2-dose schedule with a 3-month interval between doses. “The prequalification of TAK-003 is an important step in the expansion of global access to dengue vaccines, as it is now eligible for procurement by UN agencies including UNICEF and PAHO,” said Dr Rogerio Gaspar, WHO Director for Regulation and Prequalification. “With only two dengue vaccines to date prequalified, we look forward to more vaccine developers coming forward for assessment, so that we can ensure vaccines reach all communities who need it.” The WHO prequalification list also includes CYD-TDV vaccine against dengue developed by Sanofi Pasteur. AstraZeneca plans $1.5bn manufacturing facility for antibody drug conjugates in Singapore AstraZeneca has revealed plans to build a $1.5 billion manufacturing facility in Singapore for antibody drug conjugates (ADCs), enhancing global supply of its ADC portfolio. ADCs are next-generation treatments that deliver highly potent cancer-killing agents directly to cancer cells through a targeted antibody. The planned greenfield facility, supported by the Singapore Economic Development Board (EDB), will be AstraZeneca’s first end-to-end ADC production site, fully incorporating all steps of the manufacturing process at a commercial scale. Manufacturing of ADCs is a multi-step process that comprises antibody production, synthesis of chemotherapy drug and linker, conjugation of drug-linker to the antibody, and filling of the completed ADC substance. Pascal Soriot, Chief Executive Officer, AstraZeneca, said: “AstraZeneca has built an industry-leading portfolio of cancer medicines including antibody drug conjugates which have shown enormous potential to replace traditional chemotherapy for patients across many settings. Singapore is one of the world’s most attractive countries for investment given its reputation for excellence in complex manufacturing, and I am excited for AstraZeneca to locate our $1.5 billion ADC manufacturing facility in the country.” © stock.adobe.com/ Love Employee Cartography and Gilead enter into strategic collaboration agreement to develop cancer therapies Cartography Biosciences has entered into a strategic collaboration agreement with Gilead Sciences to discover and develop therapies for patients with triple-negative breast cancer (TNBC) and the most common form of non-small cell lung cancer (NSCLC), adenocarcinoma. Under the multi-year collaboration, Cartography’s proprietary computational and genomics platform will be utilized to discover and validate novel tumor-selective target antigens and pairs of antigens. Cartography’s ATLAS and SUMMIT platforms integrate single-cell data from a comprehensive healthy reference and tumor atlas – applying target identification algorithms to identify single or pairs of targets that are most specific to the intended target cells and optimized for therapeutic programs. Gilead can opt in on multiple targets identified through this collaboration and will undertake all further research, development, and commercialization of programs against those targets. Under the terms of the agreement, Cartography will receive an upfront payment of $20 million, with additional near-term preclinical milestones. Cartography is also eligible to receive development, regulatory and commercial milestones, and tiered royalties on net sales for Gilead programs against each optioned target. © stock.adobe.com/ witsawat © stock.adobe.com/. Sundry PhotographyPharma Business International 5 www.pbiforum.net Latest news Asymchem takes former Pfizer development and API pilot plant manufacturing facilities Asymchem Laboratories will operate the former Pfizer U.K. small molecule API pilot plant and part of the development laboratories through a new lease agreement between Asymchem and Discovery Park, establishing Asymchem’s first manufacturing footprint in Europe. Asymchem will continue to operate the site in Sandwich, Kent, as a clinical small molecule development and manufacturing facility to meet global client demands for pharma services and supply. The development laboratories are expected to begin operation in June 2024, followed by the API pilot plant in August. The site is expected to employ approximately 100 individuals by the end of 2024, including many staff previously employed by Pfizer. Planned additions for the site include capabilities for the manufacture of peptides and oligonucleotides, as well as sustainability capabilities utilizing continuous flow and biocatalysis. “We are excited to become a part of the European pharma manufacturing community,” said Chairman and CEO of Asymchem Group, Dr. Hao Hong. “Meeting the needs of our clients in bringing manufacturing into the Western market will continue to be part of our long-term strategy to meet overall global business demands.” © stock.adobe.com/ MichaelVi QurAlis grants Lilly exclusive global license for ALS and FTD therapy QurAlis has entered into an exclusive license agreement with Eli Lilly and Company in which QurAlis is granting Lilly global rights to develop and commercialize QRL-204, a potentially best-in-class splice-switching antisense oligonucleotide (ASO) designed to restore UNC13A function in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative diseases. Under the terms of the agreement, QurAlis granted Lilly an exclusive, worldwide license to develop and commercialize QRL-204 and other UNC13A- targeting compounds in exchange for an upfront payment of $45 million to QurAlis, plus an additional equity investment. QurAlis is also eligible for future milestone payments of up to $577 million and tiered royalties on net sales. The agreement includes a research and development (R&D) collaboration to identify and develop additional candidates targeting UNC13A, leveraging QurAlis’ proprietary FlexASO™ Splice Modulator Platform. The QurAlis FlexASO Splice Modulator Platform was developed to generate splice-switching ASOs with improved potency and increased therapeutic index. QurAlis’ ASOs correct UNC13A mis-splicing, restore UNC13A protein production and reduce cryptic exons that may contribute to disease progression. © stock.adobe.com/ LASZLO Nuvalent receives U.S. FDA breakthrough therapy designation for NVL-655 The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation (BTD) to Nuvalent’s NVL-655 for the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with two or more ALK tyrosine kinase inhibitors (TKIs). ALK rearrangements occur in up to approximately 5% of metastatic NSCLCs. At the time of diagnosis, up to 40% of these patients present with accompanying brain metastases, and approximately 50% of patients develop resistance mutations following treatment with currently available first- or second-generation ALK TKIs. There remains no clear standard of care for patients who have been previously treated with two or more ALK TKIs. NVL-655 is a novel brain-penetrant ALK-selective TKI created with the aim to simultaneously overcome the clinical challenges of emergent treatment resistance, brain metastases, and off-target central nervous system (CNS) adverse events associated with inhibition of the structurally-related tropomyosin receptor kinase (TRK) family.6 Pharma Business International www.pbiforum.net Latest news Nona Biosciences enters global license and option agreement with AstraZeneca for monoclonal antibodies Nona Biosciences has entered into a license agreement with AstraZeneca for preclinical monoclonal antibodies that will be used to create targeted therapies in oncology. Under the terms of the agreement, Nona Biosciences shall receive $19 million upon completion of the transaction. Nona is eligible to receive an additional $10 million in potential near-term milestone payments and up to $575 million upon achieving specified development, regulatory, and commercial milestones, as well as tiered royalty payments on net sales. In addition, Nona is eligible to receive payments for the option programs should AstraZeneca exercise these options. “We are delighted to announce this agreement with AstraZeneca, global leaders in developing tumor targeted therapies, to maximize the potential of our novel antibodies,” said Jingsong Wang, M.D., Ph.D., Chairman of Nona Biosciences. “This agreement further validates our leading antibody discovery platform, and we look forward to seeing our antibodies developed into potential new medicines for cancer patients.” Lilly increases manufacturing investment to $9bn at newest Indiana site Eli Lilly and Company has more than doubled its investment in its Lebanon, Indiana, manufacturing site with a new $5.3 billion commitment, increasing the company’s total investment in this site from $3.7 billion to $9 billion. This expansion will enhance Lilly’s capacity to manufacture active pharmaceutical ingredients (API) for Zepbound® (tirzepatide) injection and Mounjaro® (tirzepatide) injection so that more adults with chronic diseases like obesity and type 2 diabetes may benefit from these treatments. Since 2020, Lilly has committed more than $16 billion to develop new manufacturing sites in the U.S. and Europe. New locations outside Indiana include Research Triangle Park and Concord, North Carolina; Limerick, Ireland; and Alzey, Germany. Separately, the company has invested an additional $1.2 billion to update existing manufacturing facilities in Indianapolis and recently acquired an injectable manufacturing facility in Pleasant Prairie, Wisconsin, from Nexus Pharmaceuticals. Together, these manufacturing investments total more than $18 billion. AbbVie and Gilgamesh Pharmaceuticals to develop next-generation therapies for psychiatric disorders AbbVie and Gilgamesh Pharmaceuticals have announced a collaboration and option-to-license agreement to develop next-generation therapies for psychiatric disorders. This collaboration will leverage AbbVie’s expertise in psychiatry and Gilgamesh’s innovative research platform to discover novel neuroplastogens. Classic psychedelic compounds provide novel mechanisms to address mental health disorders, and some have shown promising clinical efficacy where other treatments have been ineffective. However, these first-generation compounds may induce profound psychoactive effects, such as hallucinations, necessitating in-office administration and concomitant supportive care. Next-generation versions known as neuroplastogens target mechanisms that have shown potential to provide significant clinical benefits and are designed to minimize the challenging effects seen with first-generation compounds. These new compounds hold substantial promise for treating a variety of psychiatric conditions, including mood and anxiety disorders. Gilgamesh has leveraged an innovative research platform to successfully identify lead compounds in this novel class of therapeutics. Jonathan Sporn, M.D., Chief Executive Officer at Gilgamesh Pharmaceuticals, said: “Our collaboration will pioneer research of a new generation of therapies that hold great potential for improving patient outcomes.” © stock.adobe.com/ Ole © stock.adobe.com / Valeriya Zankovych © stock.adobe.com / Valeriya Zankovych Biogen receives European Commission approval for QALSODY to treat rare, genetic form of ALS The European Commission (EC) has granted marketing authorization under exceptional circumstances and maintained orphan designation for Biogen’s QALSODY (tofersen) for the treatment of adults with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 gene (SOD1-ALS). QALSODY is the first treatment approved in the European Union to target a genetic cause of ALS, also known as motor neuron disease (MND). The marketing authorization for QALSODY is granted under exceptional circumstances, which is recommended when the benefit/risk assessment of a treatment is determined to be positive but due to the rarity of the disease, it is unlikely that comprehensive data can be obtained under normal conditions of use. “QALSODY’s approval represents a paradigm shift in the treatment of SOD1-ALS, offering hope to patients and loved ones who have long awaited a breakthrough,” said Philip Van Damme, M.D., Ph.D., Professor of Neurology and Director of the Neuromuscular Reference Center at the University Hospital Leuven in Belgium. “The European Academy of Neurology has confirmed new treatment guidelines for ALS that recognize QALSODY should be offered as first-line treatment for patients with SOD1- ALS.” LEQEMBI approved for treatment of Alzheimer’s disease in South Korea The Ministry of Food and Drug Safety (MFDS) in South Korea has approved Eisai and Biogen’s humanized anti-soluble aggregated amyloid- beta (A?) monoclonal antibody LEQEMBI (lecanemab) for treatment in adult patients with mild cognitive impairment due to Alzheimer’s disease (AD) or mild AD (early AD). LEQEMBI selectively binds to soluble A? aggregates (protofibrils), as well as insoluble A? aggregates (fibrils) which are a major component of A? plaques in AD, thereby reducing both A? protofibrils and A? plaques in the brain. LEQEMBI is the first and only approved treatment shown to reduce the rate of disease progression and to slow cognitive and functional decline through this mechanism. South Korea is the fourth country to grant approval, following approvals in the U.S., Japan, and China. FDA approves Amgen’s IMDELLTRA for the treatment of extensive-stage small cell lung cancer The U.S. Food and Drug Administration (FDA) has approved Amgen’s IMDELLTRA (tarlatamab-dlle) for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. IMDELLTRA has received accelerated approval based on the encouraging response rate and duration of response (DoR) observed in clinical studies. “The FDA’s approval of IMDELLTRA marks a pivotal moment for patients battling ES-SCLC. This DLL3-targeting therapy in ES-SCLC comprises a transformative option demonstrating long-lasting responses in pretreated patients,” said Jay Bradner, M.D., Executive Vice President, Research and Development, and Chief Scientific Officer at Amgen. “This approval further demonstrates our commitment to addressing aggressive cancers through our second FDA-approved Bispecific T-cell Engager (BiTE®) molecule. IMDELLTRA offers these patients who are in urgent need of new innovative therapies hope, and we’re proud to deliver this long-awaited effective treatment to them.” Zai Lab and Innoviva Specialty Therapeutics secure approval for XACDURO for hospital- acquired and ventilator-associated pneumonia in China China’s National Medical Products Administration (NMPA) has approved Zai Lab’s New Drug Application (NDA) for XACDURO (sulbactam- durlobactam) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex in patients 18 years of age and older. The World Health Organization considers Acinetobacter a top-priority pathogen worldwide that needs novel antibiotics. “The NMPA approval of XACDURO demonstrates Zai Lab’s commitment to developing and delivering innovative therapies that address high unmet medical needs for patients in China and around the world,” said Dr. Harald Reinhart, President and Head of Global Development, Neuroscience, Autoimmune & Infectious Diseases, Zai Lab. “The public threat of dangerous pan-resistant Acinetobacter infections requires urgent action, as treatment options are limited and mortality rates remain high. We believe XACDURO represents a major step forward in an area of significant patient need.” European Commission approves Celltrion’s omalizumab biosimilar Omlyclo The European Commission (EC) has approved Celltrion’s Omlyclo (CT- P39), an omalizumab biosimilar referencing Xolair. Omlyclo is approved for the treatment of allergic asthma, chronic spontaneous urticaria (CSU), and chronic rhinosinusitis with nasal polyps (CRSwNP). The decision is based on clinical evidence, including results from a global Phase III clinical trial designed to evaluate the efficacy, safety and pharmacokinetics of Omlyclo compared to the reference product Xolair in patients with CSU up to Week 40. “For more than two decades, omalizumab, a blockbuster monoclonal antibody anti-IgE, has revolutionised the management of chronic immune-mediated inflammatory diseases,” said Professor Marcus Maurer, Professor of Dermatology and Allergy, Co-Director for the Fraunhofer Site for Immunology and Allergology of the Fraunhofer Translational Medicine and Pharmacology ITMP and Executive Director for the Institute of Allergology, Charité – Universitätsmedizin Berlin, Germany. “The development of a biosimilar of omalizumab is a welcome solution to help alleviate some challenges with treatment access. The recently approved treatment Omlyclo® has a comparable efficacy, safety and immunogenicity profile to Xolair®.” www.pbiforum.netPharma Business International 7M&A ROUND-UP 8 Pharma Business International www.pbiforum.net R ecent regulator challenges make major pharma buyouts less likely as we look ahead, but that doesn’t mean the M&A landscape is not in good health. A wealth of deals, though smaller than in the past, continue to be made, with giants showing great interest in strategic strikes as patent cliffs loom. Pharma Business International shares acquisitions since our last issue. MSD - EyeBio Firstly, MSD has entered into a definitive agreement to, through a subsidiary, acquire Eyebiotech (EyeBio), a privately held ophthalmology-focused biotechnology company. Under the terms of the agreement, MSD will acquire all outstanding shares of EyeBio for up to $3 billion, including an upfront payment of $1.3 billion in cash and a further potential $1.7 billion in developmental, regulatory and commercial milestone payments. EyeBio is developing a pipeline of clinical and preclinical candidates for the prevention and treatment of vision loss associated with retinal vascular leakage, a known risk factor for retinal diseases. The company’s lead candidate, Restoret (EYE103), is an investigational, potentially first-in-class tetravalent, tri-specific antibody that acts as an agonist of the Wingless-related integration site (Wnt) signaling pathway. Based on positive results from the open-label Phase 1b/2a AMARONE study in patients with diabetic macular edema (DME) and neovascular age-related macular degeneration (NVAMD), Restoret is anticipated to advance into a pivotal Phase 2b/3 trial to investigate the treatment of patients with DME in the second half of 2024. “We continue to execute on our science-led business development strategy to expand and diversify our pipeline,” said Dr. Dean Y. Li, president, MSD Research Laboratories. “The EyeBio team, under the leadership of Dr. David Guyer and Dr. Tony Adamis, has a strong track record of developing groundbreaking ophthalmology therapies. By combining our strengths, Deals in demand Despite challenges, the pharma industry has kept its renewed interest in acquisitions. 10 Á we aim to advance with rigor and speed the development of their promising pipeline of candidates targeting retinal diseases.” Merck - Mirus Bio In a further deal, Merck has signed a definitive agreement to acquire Mirus Bio for $600 million. Mirus Bio, part of Gamma Biosciences, is a life science company that specializes in the Pharma Business International 9 www.pbiforum.net M&A ROUND-UP © stock.adobe.com/volody10Next >