Feliza Mirasol is the science editor for 

Feliza Mirasol

Circio Holding, a Norway-based biotechnology company specializing in next-generation circular RNA (circRNA) vector technology for gene therapy, announced on Nov. 19, 2024, that it has entered into a collaboration with Spain-based Certest Biotec, an independent biotechnology company focused on the development and manufacturing of 

 diagnostic products. The companies aim to develop Circio’s circVec technology into lipid nanoparticles (LNPs) to be used in formulations of therapeutics that will enable tissue-specific delivery of DNA vectors for addressing genetic disease (1).

Certest has successfully performed packaging and 

 validation of circVec–LNP formulations that are targeted for delivery to lung, liver, and spleen tissue with positive technical results. Under the collaboration, Circio will next move on to test these circVec–LNP formulations 

 over the next three to six months. The goal is to assess delivery efficiency, expression level, and durability. If the experiments are successful, they may lead to the development of multiple in-house and partnered circVec therapeutic candidates for treating genetic diseases, according to a company press release.

“Circio’s powerful circVec-DNA technology achieves more than six months durability in mouse models on a single intra-muscular injection, with up to 15-fold increase in payload expression levels vs. standard mRNA [messenger RNA]-based vector systems,” said Victor Levitsky, MD, PhD, chief scientific officer (CSO), Circio, in the press release. “Based on these promising findings 

, we are now looking for targeted delivery technology that can enable therapeutic application of circVec in specific tissues and diseases of high unmet medical need. We selected Certest as a preferred partner for circVec–LNP formulation due to the impressive tissue specificity demonstrated for their proprietary nanoparticles.”

According to the release, Certest’s proprietary ionizable lipids and optimized LNP formulations have shown notable delivery specificity to several tissues of interest for Circio (lung, liver, and spleen). In addition, technical formulation and 

 analysis of circVec–LNP formulations by Certest have been successful, allowing the companies to advance to 

“The library of ionizable lipids developed by our team is engineered for a wide range of nucleic acid payloads, exhibiting a great delivery capacity in preclinical studies and allows the production of thermostable LNPs,” said Juan Martínez Oliván, PhD, CSO of Certest Pharma, specialized unit in nucleic acids delivery systems at Certest Biotec, in the press release. “Our capability to passively target different tissues unlocks the possibility to treat organ-specific diseases. We are very enthusiastic about the joint formulation of Circio’s new approach to circular RNA vector technology with our versatile ionizable lipids, creating a unique LNP-strategy for gene therapy treatment.”

Circio’s proprietary circVec technology is based on a modular genetic cassette design, which allows for efficient biogenesis of multifunctional circRNA from DNA and viral vectors. This circRNA can be deployed in multiple disease settings, including cell and gene therapy and chronic diseases, according to the press release. CircRNAs are a class of single-stranded RNAs that are being engineered as novel treatments for disease treatment and prevention (2).

1. Circio Holding. Circio Announces circVec LNP-delivery Collaboration with Certest Progressing to 

 Testing. Press Release. Nov. 19, 2024.
2. Niu, D.; Wu, Y.; Lian, J. Circular RNA Vaccine in Disease Prevention and Treatment. 

Articles

The companies will collaborate to create and test circVec DNA–LNP formulations for use in potential therapeutic applications.

Circio and Certest to Collaborate on LNP Formulations

Contract research organization BioPharmaSpec, which specializes in discovery and preclinical characterization of biopharmaceuticals, has officially launched three new European facilities in Freiburg, Germany; Bergamo, Italy; and Vilnius, Lithuania. These new facilities will focus on discovery and R&D services, according to a Nov. 12, 2024 company press release (1).

The facilities will offer structural and physicochemical characterization services for a variety of biopharmaceutical products, including monoclonal antibodies, antibody-drug conjugates, cell and gene therapy products, bioactive peptides, oligonucleotides, and carbohydrates. The company will also offer host cell protein identification and the quantitation of other relevant product- and process-related impurities at these facilities.

"Complementing a long career in academia where I’ve been the professor of Biological Chemistry at Imperial College since 1980, it has been a privilege to help drive forward this exciting development and significant expansion of BioPharmaSpec. The Freiburg, Bergamo, and Vilnius sites join our existing UK [United Kingdom] and US-based facilities to create the BioPharmaSpec Group of companies, serving the global biopharmaceutical industry,” said Prof. Howard R. Morris FRS, founder of the BioPharmaSpec Group of companies, in the press release (1).

The launch of these new facilities marks a significant milestone in BioPharmaSpec’s growth since it was founded in 2014 by Morris—who brought with him 45 years of experience in mass spectrometry discoveries and who was the founder of the M-Scan Group of companies—and Andrew Reason, PhD—who brought with him 25 years of experience in commercialization of analytical methods and who previously held the role of group manager of the European M-Scan laboratories. BioPharmaSpec now serves biopharmaceutical companies worldwide with its structural and physicochemical characterization services, which facilitates progress of drug pipelines, according to the press release (1).

“With the opening of these new laboratories in January 2025 and recruitment of local expert scientists, we are strategically and uniquely placed to provide our expanding global client base with the highest levels of technical and customer service," said Lindsay McGowan, director of business development at BioPharmaSpec, in the press release (1).

In addition to modern office space and meeting rooms, the new laboratories at the three facilities will host state-of-the-art instrumentation, Including accurate mass quantitation systems from Waters and SCIEX. (e.g., Waters Select Series CYCLIC ion mobility separation (IMS) high-definition liquid chromatography tandem mass spectrometry (LC–MS/MS) with electron capture dissociation, SCIEX ZenoTOF 7600 LC–MS/MS with electron-activated dissociation, Waters Xevo TQ Absolute, and Waters Xevo G3 LC–MS/MS quadrupole time-of-flights). The use of these high-end instruments combined with support from expert scientific advice, will enable access to high-quality structural characterization services with fast turnaround times, the company stated in its press release (1).

The company has also published recruitment announcements for scientists and technicians for the Vilnius and Freiburg sites (2,3).

1. BioPharmaSpec. BioPharmaSpec Announces Three New Facilities in Freiburg, Bergamo and Vilnius. Press Release. Nov. 12, 2024.
2. BioPharmaSpec. BioPharmaSpec is Recruiting: Scientists and Technicians- BSc or PhD (Vilnius, Lithuania). Press Release. Nov. 11, 2024.
3. BioPharmaSpec. BioPharmaSpec is Recruiting: Scientist- Masters or PhD (Freiburg, Germany). Press Release. Nov. 11, 2024.

Located in German, Italy, and Lithuania, the new European facilities  will specialize in drug discovery and R&D services. 

Three New European Facilities Established by BioPharmaSpec for R&D

SEKISUI Diagnostics has completed a £15.7 million (US$20.7 million) expansion of its current good manufacturing practice (CGMP) capacity at its UK site for its microbial contract development and manufacturing business (CDMO), BioProduction by SEKISUI. The company plans to use the expanded capacity for the manufacture of clinical-grade drug substances, according to a Nov. 14, 2024 company press release.

Following appropriate licensure, the expanded capacity will enable the CDMO business’ manufacturing capabilities for common drug types, including enzymes, proteins, and antibody fragment therapies as well as plasmids and enzymes for gene therapy manufacture. BioProduction by SEKISUI is a fermentation-focused CDMO. The business has expertise in proteins and downstream purification, and its microbial process development and production experience facilitates technical transfer and process scale-up. The recent expansion includes new Grade C microbial fermentation and purification suites that will accommodate production scales up to 1000 L.

“This investment supports the vision and mission of SEKISUI Diagnostics and the broader SEKISUI Medical Group by enabling the continued growth of our share of the biologics CDMO market,” said Robert Schruender, president and CEO of SEKISUI Diagnostics, in the press release (1). “We look forward to working with biopharma companies seeking an experienced partner at a time when demand is outstripping manufacturing capacity.”

A part of SEKISUI Medical Group, SEKISUI Diagnostics has over 40 years of experience supplying innovative medical diagnostics globally to physicians, hospitals, laboratories, and alternate testing locations. Its product lines include clinical chemistry reagents, point-of-care tests, pre-analytic systems, and enzymes and specialty biochemicals as well as its offerings in its microbial CDMO business.

“Over many years we have honed our technical and operational competency and expertise in enzyme production and microbial fermentation to serve our partners globally. This CGMP expansion enables us to support a broader customer base and expand our offering to existing customers,” said Louise Digby, vice-president, Enzymes & BioProduction, SEKISUI Diagnostics in the press release (1).

It has been noted that many companies ranging from biotech startups working on early-phase biologics to mature companies with products in commercial production have switched 

from mammalian cell culture to microbial fermentation

. The switch has been largely attributed to the cost-savings that microbial expression systems bring. Microbial expression systems have also demonstrated that they are well built for newer modalities such as messenger RNA (mRNA) and cell and gene therapies. Furthermore, microbial fermentation offers shorter production runs that can be completed in days instead of weeks, compared to mammalian cell culture (2).

However, microbial fermentation poses its own challenges, such as the need to maintain sufficient oxygen transfer while removing metabolic heat. Such challenges are being addressed via equipment changes, facility design, and process development (2).

1. SEKISUI Diagnostics. SEKISUI Completes £15.7 Million Expansion in cGMP Biopharma CDMO Capacity. Press Release. Nov. 14, 2024.
2. Graham, C.; Awang, G. 

High-Growth Microbial Fermentation for the Manufacture of Biologics

SEKISUI has used a £15.7 million (US$20.7 million) investment to expand its clinical-grade drug substance manufacturing at its UK site. 

CDMO SEKISUI Expands its CGMP Biopharma Manufacturing Capacity

Clinical-stage biotechnology company Alentis Therapeutics (Alentis), which specializes in developing treatments for Claudin-1 positive (CLDN1+) tumors and organ fibrosis, announced that it has raised $181.4 million in Series D financing. The financing was supported by a syndicate of top-tier biotech investors. OrbiMed led the way, with Novo Holdings and Jeito Capital as co-leads. This financing will support Alentis’ efforts to develop a significant pipeline of CLDN1-targeted antibody-drug conjugate (ADC) drugs for treating solid tumors, according to a Nov. 12, 2024 press release (1).

In addition to the lead investors, new investors such as Frazier Life Sciences, Longitude Capital, Catalio Capital, Piper Heartland Healthcare Capital, and Avego Bioscience Capital contributed to the financing, while existing investor RA Capital Management also provided significant backing, along with support from Morningside Venture Investments, BB Pureos, Bpifrance (via its InnoBio 2 fund) as well as other early institutional investors.

“This financing is a testament to the transformational potential of CLDN1 [ADCs] for the treatment of solid tumors,” said Roberto Iacone, chief executive officer of Alentis, in the company press release. “Let me take this opportunity to extend a warm welcome to our new investors. We’re excited to execute our development strategy and deliver clinical data for our programs over the next 12–18 months.”

The company intends to use proceeds from the financing to conduct Phase I/II clinical trials of ALE.P02 and ALE.P03, two ADCs targeting CLDN1, as well as conduct further development of its pipeline. Some of the proceeds will go toward general corporate purposes. FDA cleared an investigational new drug application for a Phase I/II clinical trial of ALE.P02 (with a tubulin inhibitor) to study the ADC candidate in advanced or metastatic CLDN1+ squamous solid tumors. This trial is expected to begin in the first quarter of 2025. Meanwhile, ALE.P03 (with a topoisomerase I inhibitor) is expected to begin a first-in-human trial in patients with CLDN1+ tumors in 2025.

“With this financing, Alentis is now well positioned to advance its CLDN1 antibody-drug conjugates, which have the potential to be first and best-in-class therapies for the treatment of cancer,” said Dina Chaya, partner at OrbiMed, in the press release.

“ADCs have shown their potential to be highly effective cancer treatments,” added Naveed Siddiqi, senior partner, Novo Holdings, Venture Investments, in the release. “Alentis has an exciting pipeline of first-in-class ADCs, and we are proud to have co-led this round. We are looking forward to seeing the data generated from the first clinical trials of ALE.P02 and ALE.P03.”

In addition, three new board members have been appointed as part of the financing and will join the Alentis board of directors. The three new board members are Chaya, who has over 20 years of experience in healthcare investments with a focus on biopharma and medical technology; Anna Chen, principal at Frazier Life Sciences, who has been involved in the investment and building of many of Frazier Life Sciences’ biopharmaceutical portfolio companies over the past seven years; and Brian Liu, managing director at Longitude Capital, who brings more than 10 years of biopharma consulting and investing experience, with a focus on transformative healthcare innovation.

1. Alentis Therapeutics. Alentis Therapeutics Raises $181.4 Million in an Oversubscribed Series D Financing to Advance the Clinical Development of Anti-Claudin-1 ADCs in Solid Tumors. Press Release. Nov. 12, 2024.

Financing from OrbiMed, Novo Holdings, Jeito Capital, and others will enable Alentis Therapeutics to advance its pipeline of Claudin-1-targeted ADCs for treating solid tumors.

Alentis Therapeutics to Advance Anti-Claudin-1 ADCs to Treat Solid Tumors on $181.4 Million Financing

 (Kebilidi, PTC Therapeutics) on Nov. 14, 2024. Eladocagene exuparvovec-tneqan is an adeno-associated virus vector-based gene therapy for treating adult and pediatric patients with aromatic L-amino acid decarboxylase (AADC) deficiency (1). According to FDA, Kebilidi is the first FDA-approved gene therapy indicated for this disease.

Administration of the gene therapy is performed via four infusions during one surgical session into a large structure in the brain that is involved in motor control. FDA noted in its press release that Kebilidi should be administered in a medical center that specializes in pediatric stereotactic neurosurgery, which is a technique that uses imaging and special equipment to deliver therapies to specific areas in the brain. Following infusion, the treatment leads to expression of AADC and a subsequent increase in the production of dopamine, which is a critical neurotransmitter in the brain associated with movement, attention, learning and memory, according to the press release.

“Clinical advancements in the field of gene therapy continue to lead to the discovery and availability of innovative treatment options for rare diseases that are otherwise difficult to manage,” said Peter Marks, MD, PhD, director of FDA’s Center for Biologics Evaluation and Research (CBER), in the release (1). “Today’s approval underscores our commitment to help make safe and effective treatments available for patients in need.”

AADC deficiency is a rare genetic disorder that affects the production of some neurotransmitters, interfering with the body’s nervous system cells’ ability to communicate with each other. Symptoms include delays in gross motor function (head control, sitting, standing, and walking), hypotonia (weak muscle tone), and developmental and cognitive delays.

“AADC deficiency can cause a range of debilitating symptoms, including life-threatening complications,” said Nicole Verdun, MD, director of the Office of Therapeutic Products in CBER, in the release (1). “[The] approval represents important progress in the advancement and availability of safe and effective treatments for debilitating genetic disorders.”

Eladocagene exuparvovec-tneq’s safety and effectiveness were demonstrated in an open-label, single-arm clinical study with 13 pediatric patients who had confirmed diagnoses of AADC deficiency. All patients at the start of the study were noted as having no gross motor function (the most severe presentation of AADC deficiency) and decreased AADC activity in the plasma. The patients treated with eladocagene exuparvovec-tneq were compared to untreated patients (natural history). At week 48 following treatment, motor milestone assessments were completed for 12 of the 13 patients. The efficacy of the gene therapy was demonstrated by evidence of improved gross motor function in eight out of 12 patients treated that was not reported in untreated patients with the severe presentation of AADC deficiency.

Eladocagene exuparvovec-tneq underwent an accelerated approval process, and its application received priority review, orphan drug designation, and was granted a rare pediatric disease priority review voucher by FDA. Continued approval for the AADC deficiency indication may be contingent upon the agency receiving verification and description of the clinical benefit of the product, such as the durability of improved symptoms, in a confirmatory clinical trial. Eladocagene exuparvovec-tneq is in an ongoing confirmatory trial to verify its clinical benefit.

In addition to the gene therapy product’s approval, FDA also authorized an infusion tube, the SmartFlow Neuro Cannula (ClearPoint Neuro) (2), which is inserted into a target in the brain (parenchymal tissue), for delivering eladocagene exuparvovec-tneq. FDA stated in its release that the SmartFlow Neuro Cannula is currently the only FDA authorized device indicated for use in the administration of eladocagene exuparvovec-tneq.

FDA Approves First Gene Therapy for Treatment of Aromatic L-amino Acid Decarboxylase Deficiency

. Press Release. Nov. 14, 2024.
2. ClearPoint Neuro. ClearPoint Neuro Announces FDA De Novo Marketing Authorization of SmartFlow Cannula for Direct Delivery of Gene Therapy to the Brain. Press Release. Nov. 13, 2024.

FDA's approval of eladocagene exuparvovec-tneq (Kebilidi) makes that product the first FDA-approved gene therapy for treating AADC deficiency.

PTC Therapeutics Gains FDA Approval for AADC Deficiency Gene Therapy

Frontier Scientific Solutions, a temperature-controlled storage and transportation company that exclusively serves the life sciences industry, announced on Nov. 13, 2024 that it has established state-of-the-art current good manufacturing practice (CGMP) facilities at Wilmington International Airport (ILM) in North Carolina, United States, and Shannon Airport (SNN) in County Clare, Ireland. The strategic locations will enable the company to create the first life sciences-dedicated direct global gateway, according to a company press release. Supported by a $1.5 billion commitment from an investor, the gateway is central to Frontier Scientific Solutions’ goal to create streamlined shipping lanes—starting with a route between North America and Europe—specifically for time- and temperature-sensitive pharmaceutical and biopharmaceutical products.

These facilities are supported by the $1.5 billion funding from GID, a real estate investor, owner, operator, and developer. Frontier Scientific Solutions expects that the facilities in both locations will bring further financial and supply chain management benefits through designation as Free Trade Zones (FTZ). The company unveiled plans at ILM for the scale and impact of its global gateway model. The company expects that this model will enable companies in the life sciences industry to transport time- and temperature-sensitive materials in significantly shorter timeframes. Benefits include fewer touchpoints, less risk, and more sustainable operations.

"We are thrilled to announce this transformative partnership with the airports at Wilmington and Shannon, enabled by GID's investment,” said Steve Uebele, CEO of Frontier Scientific Solutions, in the company press release. “Our initiative disrupts the life science supply chain market—promoting zero product losses, increasing sustainability, and directly saving lives—and it marks the first step in Frontier's goal to become the market-leading solutions provider."

The funding will be used for the construction of CGMP-compliant, temperature-controlled storage facilities housed at Shannon and within the FTZ at Wilmington. Having FTZ designation will facilitate streamlined customs and FDA processing, duty deferral, and operational efficiencies, all of which are critical for the efficient and secure distribution of life sciences products across international borders, the company stated in the release.

"GID’s commitment underscores our dedication to developing cutting-edge infrastructure that meets the specialized needs of the life sciences industry,” said Greg Bates, president and CEO of GID, in the release. “The new facilities in Wilmington and Shannon will create an unparalleled logistics network between the US and Europe, empowering companies to deliver critical healthcare products with unmatched speed and precision."

Based on live case studies conducted by Frontier Scientific Solutions, it was consistently demonstrated that a reduction of days to weeks in the transportation and waiting times for temperature-sensitive shipments were achieved with its gateway model. “Providing the industry with direct distribution makes this global gateway model faster, reducing exposure to temperature excursions, risk from unnecessary touchpoints, and carbon emissions. It will set a new benchmark for quality, speed, and environmental responsibility,” the company stated in the press release.

The facilities at ILM and SNN will be linked by a direct lane dedicated exclusively to life sciences materials. Flight operations are slated to begin early in 2025. Frontier Scientific Solutions also offers a fast direct-ocean lane from North Carolina to Cork, Ireland, and can achieve delivery in 12 days via this route. This new infrastructure will allow the company to disrupt the market by enabling faster deliveries while reducing reduced risk.

In addition to supply chain logistics, the biopharma industry is seeking ways to minimize risks in providing temperature-sensitive molecules to patients, such as 

innovating product formulation and drug delivery systems

Prioritizing Formulation Strategies for Temperature-Sensitive Biotherapeutics

Pharmaceutical Technology Trends in Formulation

Frontier Scientific Solutions has unveiled plans to use a $1.5 billion commitment from a major investor to create a global free trade zone gateway to facilitate the life sciences supply chain using Wilmington International Airport in North Carolina.