Feliza Mirasol

In this episode of Drug Digest, industry experts discuss their experiences in dealing with the challenges of developing and manufacturing next-generation biotherapeutics as well as triumphs that move the industry as a whole forward.

Challenges and Triumphs in Next-Generation Biotherapeutic Development

The development of next-generation biotherapeutics is in full swing, which means that developers and biomanufacturers are tackling new challenges in the drug development and manufacturing lifecycle. Two areas of focus are in the maintenance of an aseptic environment throughout the manufacturing process and the search for solutions to establishing alternative drug delivery methods that don’t require a parenteral route of administration. In this episode of 

, experts from N4 Pharma and Cellular Origins discuss their experiences in dealing with these challenges, as well as triumphs in creating innovations to move the industry as a whole forward.

Nigel Theobald is CEO of N4 Pharma, a specialist pharmaceutical company developing novel delivery systems for oncology, gene therapy and vaccines. Theobald has over 25 years’ experience in healthcare, in building businesses, strategy development and implementation, and in a strong network covering all aspects of pharmaceutical product development and commercialization. He was the head of healthcare brands at Boots Group plc in 2002 before leaving to set up a series of successful businesses, including Oxford Pharmascience Group plc, which he grew over five years into an AIM-quoted company with a market capitalization of £40 million (US$53 million) upon departure. Theobald formed N4 Pharma in 2014.



Dan Strange, PhD, Chief Technology Officer, Cellular Origins

Dan Strange has been working at the intersection of engineering and biology for almost 15 years, and he is an inventor on 20 patents. After completing a PhD in regenerative medicine at the University of Cambridge, he moved to TTP where he developed complex drug delivery devices. He was instrumental in the creation of multiple technology platforms successfully licensed to large pharma in deals worth over $100 million. For the past four years, Strange has focused on cell therapy manufacturing equipment. Strange is an active member of various automation working groups and was a reviewer on the Alliance for Regenerative Medicines A-Cell report on cell therapy manufacturing.

Drug Digest is a tech talk video series with the 

® editors, who interview industry experts to discuss the emerging opportunities, obstacles, and advances in the pharmaceutical and biopharmaceutical industry for the research, development, formulation, analysis, upstream and downstream processing, manufacturing, supply chain, and packaging of drug products.

Innovations in Biopharmaceutical Development

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Drug Digest: Challenges and Triumphs in Next-Generation Biotherapeutic Development

Novo Nordisk announced on Dec. 16, 2024 that it will invest DKK 8.5 billion (US$1.2 billion) to build a new production facility in Odense, Denmark, for the manufacture of multiple product types for treating rare diseases, such as hemophilia, both at present and in the future. This is the first investment Novo Nordisk has made for breaking new ground in Denmark in this century, the company stated in a press release.

The new site will include a state-of-the-art finished production facility and warehouse spanning more than 40,000 m

. The production facility will be designed to be modular and flexible to enable the manufacture of multiple rare disease-treating products.

"The facility will utilize advanced technology and innovative equipment to ensure the highest quality to patients and meet the growing global demand for our life-changing medicines,” said Henrik Wulff, executive vice-president, Product Supply, Quality & IT of Novo Nordisk, in the press release (1). “We are proud to build on our heritage in Denmark and look forward to embarking on this journey in Odense, a well-connected city with a dynamic community and talented workforce."

The new facility will be built with an eye toward preserving the nature in the area. More than 4000 new trees will be planted at the site, and buildings will be equipped with solar panels for enhancing on-site electricity generation. In addition, the landscape will be designed by reusing excess soil, wooden materials, and other sustainable resources to create lakes, forests, and community spaces that will be open to the public, the company stated in its release.

Construction work has begun, and completion is expected in 2027. More than 400 permanent jobs are expected to be created upon completion of the facilities, and up to 1000 external employees will be working on-site during construction.

Meanwhile, as of Dec. 14, 2024, all regulatory closing conditions related to the review of Novo Holdings’ pending acquisition of Catalent have been fulfilled, including expiry of the timing agreement in the United States, which means the parties are now free to close the transaction (2). With the close of the transaction, Novo Nordisk will fulfill its subsequent 

acquisition of three Catalent manufacturing sites

 from Novo Holdings, which Novo Nordisk originally announced in February 2024 (3). Novo Nordisk will also be acquiring Novavax’s manufacturing site in the Czech Republic, which was announced earlier in December 2024 (4).

1. Novo Nordisk. Nordisk Invests DKK 8.5 Billion in New Production Facility in Odense, Denmark. Press Release. Dec. 16, 2024.
2. Novo Nordisk. Novo Nordisk A/S: The Acquisition of Catalent by Novo Holdings, and the Related Acquisition by Novo Nordisk of Three Manufacturing Sites from Novo Holdings, is Cleared To Close. Press Release. Dec. 14, 2024.
3. Novo Nordisk. Novo Nordisk to Acquire Three Fill-Finish Sites from Novo Holdings A/S in Connection with the Catalent, Inc. Transaction. Press Release. Feb. 5, 2024.
4. Novavax. Novavax Announces Sale of Czech Republic Manufacturing Site to Novo Nordisk for $200 Million. Press Release. Dec. 4, 2024.

Articles

Novo Nordisk will use the DKK 8.5 billion (US$1.2 billion) to build a new modular and flexible production facility in Odense, Denmark, that will produce multiple products for rare diseases. 

Novo Nordisk to Establish New Production Facility for Rare Disease Therapies in Denmark with DKK 8.5 Billion Investment

In this episode of Drug Digest, industry experts discuss the ongoing development of automating biomanufacturing processes, including its challenges and practical applications. 

From Theory to Reality: Automating Process Development

The biopharmaceutical industry has seen the use of automated technologies in biomanufacturing processes grow over the years from theory to reality. In this episode of 

, industry experts discuss the ongoing advancement of automation in the biopharmaceutical industry. They give insight into how automated technologies are put to use today and how they are streamlining process development, with an eye toward saving cost, time, and manufacturing footprint.

John Hatzis, Global Life Sciences Industry Consultant, Rockwell Automation

John Hatzis has been with Rockwell Automation for ten years where he has leveraged his expertise using Rockwell technology in a variety of applications in the Life Sciences industry. He works with BiofabUSA consulting on control systems for new tissue therapies. John has a BSc in Chemical Engineering from Worcester Polytechnic Institute.


Smriti Khera, Global Head of Life Sciences Strategy and Marketing, Rockwell Automation

Smriti Khera is the global head of Life Sciences Strategy and Marketing at Rockwell Automation. She holds a PhD in Pharmaceutical Sciences from the University of Arizona, where her focus was drug discovery from natural products. After working as a pharma research scientist, she pivoted to strategic marketing to increase her impact. Over the past 12 years she has held strategy and marketing leadership roles with increasing levels of responsibilities at both Fortune 500 and early stage startups. She is passionate about leveraging her unique expertise to generate sustained impact across healthcare and life sciences using automation and digital technologies.

This episode of Drug Digest is sponsored by:

Solid Dosage Drug Development and Manufacturing

Drug Digest: From Theory to Reality: Automating Process Development

Genentech, a member of the Roche Group, has entered into a license agreement worth nearly up to $2 billion potentially, with Sangamo Therapeutics, a genomic medicine company. Through the deal, Genentech aims to develop genomic medicines for treating certain neurodegenerative diseases via intravenous administration. Sangamo is giving Genentech an exclusive license to its proprietary zinc finger repressors directed to the tau gene and its neurotropic adeno-associated virus (AAV) capsid, STAC-BBB, for tau and a second neurology target.

Under the agreement, Sangamo will be responsible for completing a technology transfer to Genentech and will be responsible for certain preclinical activities. For its part, Genentech will be responsible for all clinical development, regulatory interactions, manufacturing, and global commercialization. Genentech expects to pay Sangamo $50 million in near-term upfront license fees and milestone payments. In addition, Sangamo is eligible to receive up to $1.9 billion in development and commercial milestones. These milestone payments would be spread across multiple potential products developed under the agreement. Sangamo is also eligible to receive tiered royalties on net sales of any products resulting from the collaboration, subject to certain specified reductions.

“Sangamo has been pioneering the field of genomic medicine for years to address devastating neurodegenerative diseases with limited current treatment options,” said Sandy Macrae, CEO, Sangamo, in the press release. “We strongly believe in the power of our zinc finger technology to regulate the expression of key genes involved in disease. The recent discovery of our industry-leading intravenously delivered AAV capsid, STAC-BBB, has the potential to address longstanding challenges in delivering therapeutics to the central nervous system. We are excited to share this powerful combination with Genentech to advance potential treatment options for devastating neurodegenerative disorders, and we are hopeful this could be the first of multiple capsid collaborations to come with other partners.”

The tau gene is critically involved in Alzheimer’s disease (AD) and other tauopathies (1). Genentech’s access to Sangamo’s zinc finger repressors will allow Genentech to develop genomic therapeutics against AD as well as an undisclosed second neurology target. Sangamo’s STAC-BBB has demonstrated potent blood-brain barrier penetration and brain transduction in nonhuman primates, the company said in the release.

“We are uniquely positioned with our collective experience, expertise, and resources in neurological research to explore transformative approaches, including gene therapy, that treat neurodegenerative diseases,” said Boris L. Zaïtra, head of Roche Corporate Business Development, in the release. “Through groundbreaking research and partnerships with companies such as Sangamo, we are committed to pursuing important breakthroughs in both early diagnosis and treatment. Our relentless pursuit of scientific innovation is taking us into areas of enormous unmet medical need and progress in treating diseases of the brain and nervous system.”

1. Medeiros, R.; Baglietto-Vargas, D.; LaFerla, F. M. The Role of Tau in Alzheimer's Disease and Related Disorders. 

 (5), 514–524. DOI: 10.1111/j.1755-5949.2010.00177.x

Genentech will have access to Sangamo’s capsid delivery platform and epigenetic regulation capabilities to develop genomic medicines for certain neurodegenerative diseases.

Genentech Enters an Approximately $2 Billion Deal to License Sangamo Therapeutics Technologies for Developing Neurodegenerative Disease Therapeutics

 On May 27, 2024, FDA granted priority review status to a supplemental biologics license application (sBLA) submitted by Sanofi for the use of Sarclisa (isatuximab) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for treating patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM).

If approved in this indication, Sarclisa would be the first anti-CD38 therapy to be used in combination with VRd, a standard of care, in newly diagnosed patients who are ineligible for a transplant, Sanofi stated in a company press release. This would be the third indication for Sarclisa in multiple myeloma if the sBLA is approved. FDA has a target action date for its decision on Sept. 27, 2024. A regulatory submission for this same indication is also under review in the European Union (EU).

“Despite recent advancements in multiple myeloma treatment, there remains a significant unmet need for new frontline therapies, particularly for transplant-ineligible patients who can face poor outcomes from the disease. The filing acceptances, as well as [FDA’s] [p]riority [r]eview designation, reinforce our confidence in Sarclisa as a potential best-in-class treatment and represent a critical step toward advancing this combination in a difficult-to-treat cancer,” said Dietmar Berger, MD, PhD, chief medical officer, global head of development, Sanofi in the release.

Both the sBLA and the filing in the EU are based on positive results from a Phase III clinical study (IMROZ), which evaluated the investigational use of Sarclisa in combination with VRd. The study met its primary endpoint, as reported by the company in December 2023 (1). A planned interim analysis of efficacy data showed that Sarclisa in combination with VRd demonstrated a statistically significant improvement in progression-free survival (PFS) compared with VRd alone in transplant-ineligible patients with NDMM. Sanofi researchers also observed that the safety and tolerability of Sarclisa in the Phase III study were consistent with the established safety profile of Sarclisa and VRd.

Sarclisa, a monoclonal antibody (mAb), binds to a specific epitope on the CD38 receptor on multiple myeloma (MM) cells to induce distinct antitumor activity. Sanofi stated in its press release that “[i]t is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activities. CD38 is highly and uniformly expressed on the surface of MM cells, making it a potential target for antibody-based therapeutics such as Sarclisa.”

Sarclisa is currently approved in more than 50 countries, including the United States and the EU, in combination with pomalidomide and dexamethasone for treating certain patients with relapsed refractory MM (RRMM) who have had two or more prior therapies, including lenalidomide and a proteasome inhibitor, and who progressed on last therapy. The mAb is also approved in 50 countries, including in the US, in combination with carfilzomib and dexamethasone, for treating patients with RRMM who have had one to three prior lines of therapy, and in the EU for patients with MM who have received at least one prior therapy.

Sarclisa is also in multiple ongoing Phase III clinical studies in combination with current standard treatments across different MM indications and is under investigation for treating other hematologic malignancies. According to Sanofi, the product’s safety and efficacy has not been evaluated by any regulatory authority outside of its approved indication.

1. Sanofi. Press Release: Sarclisa (isatuximab) Plus KRd Significantly Improved Rate of Minimal Residual Disease Negativity in Transplant-Eligible Patients with Newly Diagnosed Multiple Myeloma versus KRd Alone. Press Release, Dec. 11, 2023.

FDA granted priority review to Sanofi's sBLA for Sarclisa in combination with VRd in treating transplant-ineligible patients who are newly diagnosed with multiple myeloma.

Sanofi Gets Priority Review Status for sBLA Seeking Approval of Sarclisa in Combination Therapy for Multiple Myeloma

Merck KGaA, Darmstadt, Germany, will acquire Mirus Bio, a US-based life science company, in a $600 million deal, or approximately €550 million, according to a May 22, 2024 announcement. Pending regulatory clearance and other customary closing conditions, the transaction is expected to close in the third quarter of 2024.

The acquisition will strengthen Merck KGaA’s offerings in the viral vector manufacturing sector because Mirus Bio specializes in the development and commercialization of transfection reagents. Transfection reagents are used to introduce genetic material into cells and play a key role in producing viral vectors for use in cell and gene therapies (CGTs), according to a company press release.

“This strategic acquisition is a further building block for accelerating growth in the break-through technologies of the future. As a leader in the production of viral vectors, our goal is to make the significant potential of cell and gene therapy available for patients worldwide,” said Belén Garijo, chair of the executive board and CEO of Merck KGaA, Darmstadt, Germany, in the company press release.

The Mirus Bio acquisition represents an important step towards Merck KGaA’s goal to offer solutions for every step of viral vector manufacturing for the advancement of CGTs, from preclinical through commercial production, the company stated in the press release. Merck KGaA’s services cover a variety of viral vector types, including adeno-associated virus, lentivirus, and adenovirus. Additionally, the company offers both contract testing services and a range of comprehensive contract development and manufacturing services for viral vector manufacturing.

According to the company, the global market for process products for novel modalities such as CGTs, antibody-drug conjugates, and messenger RNA (mRNA) is expected to grow by approximately 20% per year over the mid-term (i.e., within 10 years). The overall number of CGTs in development has doubled since 2019, and more candidates are advancing to the commercial stage, for example.

“Novel modalities, such as viral vector-based cell and gene therapies, hold immense promise to improve the lives of patients. Combining Mirus Bio's leading technology with our bioprocessing expertise and portfolio allows us to provide solutions for almost every step of viral vector development and manufacturing,” said Matthias Heinzel, member of the executive board of Merck KGaA, Darmstadt, Germany, and CEO Life Science, in the press release. “With our integrated offering along the viral vector value chain, we are now well-positioned to support our customers in this fast-growing market to positively impact the lives and health of patients worldwide.”

Viral vectors are a key component in the production of these therapies. Thus, to support that growth, Merck KGaA opened its second Carlsbad, Calif.-based viral vector contract development manufacturing facility in 2021 (1). The company invested €100 million (US$108 million) in the site, which more than doubled the company’s capacity for supporting large-scale commercial and industrial manufacturing for viral vector-based gene therapies.

In addition to its second viral vector manufacturing facility, Merck KGaA also continues to invest in R&D that will enable new therapeutics to be brought to market. In April 2024, the company announced it was investing more than €300 million (US$325 million) to establish a new life science research center at its global headquarters in Darmstadt (2). The investment will harness research on key technologies for the manufacture of antibodies, novel modalities such as CGTs and mRNA applications, and additional products required for biotechnological production.

“We have been driving innovation in nucleic acid delivery for two decades,” said Dale Gordon, CEO of Mirus Bio, in the press release. “The broad portfolio, scale, and global reach of Merck KGaA, Darmstadt, Germany, combined with our leading transfection reagents, will help take our business to even greater heights and allow us to serve more customers, and ultimately patients, worldwide.”

1. Merck KGaA. Merck KGaA, Darmstadt, Germany, Completes New Viral Vector Contract Development Manufacturing Facility for Gene Therapy. Press Release, Oct. 12, 2021.
2. Merck KGaA. Merck KGaA, Darmstadt, Germany, Invests More Than € 300 Million in New Life Science Research Center. Press Release, April 25, 2024.

With this acquisition, Merck KGaA will have the capability to offer integrated services for viral vector manufacturing.