More complex and challenging compounds require a tailored formulation approach.

Unique Molecules Push Formulation Boundaries

EUA for Lilly's mAb treatment; Pifzer reports 90% vaccine efficacy in interim results

COVID-19 Therapy Developments

On Nov. 23, 2020, ARCA biopharma, a US-based biopharmaceutical company specializing in a precision-medicine approach to developing cardiovascular therapeutics, announced that FDA has granted fast track designation for its investigational compound, AB201, a small recombinant fusion protein, for the potential treatment of COVID-19.

The company plans to initiate a Phase IIb clinical trial in December 2020 of the compound in approximately 100 patients hospitalized with COVID-19, with topline trial data anticipated in the second quarter of 2021. AB201 is a potent, selective inhibitor of tissue factor (TF), which plays a central role in the inflammatory response to viral infections.

“Fast [t]rack designation for the AB201 development program is an important acknowledgement of the critical need for treatments for hospitalized COVID-19 patients, whether effective vaccines are approved and available or not,” said Dr. Michael Bristow, ARCA’s president and CEO, in a company press release. “We believe AB201’s combination of anticoagulant, anti-inflammatory, and antiviral effects may favorably impact clinical recovery of patients hospitalized with COVID-19 and look forward to beginning the ASPEN-COVID-19 trial to evaluate AB201’s potential efficacy in this patient population.”

Articles

FDA granted fast track designation for AB201, a small recombinant protein that is a potent, selective inhibitor of tissue factor, for the potential treatment of COVID-19. 

FDA Grants Fast Track Designation to ARCA biopharma’s Potential COVID-19 Treatment

Bristol Myers Squibb announced on Nov. 24, 2020 that the European Commission (EC) approved Opdivo (nivolumab), a programmed death-1 immune checkpoint inhibitor, for the second-line treatment of unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) in adults who have had prior fluoropyrimidine- and platinum-based combination chemotherapy.

The EC’s decision is based on results from a Phase III study (sponsored by Ono Pharmaceutical, Japan) that demonstrated a statistically significant and clinically meaningful improvement in overall survival in patients who received Opdivo versus chemotherapy. The safety profile for Opdivo was favorable compared with chemotherapy and consistent with previously reported studies of Opdivo in other solid tumors, Bristol Myers Squibb reported in a company press release.

“Today’s approval marks a critically important milestone for those living with esophageal squamous cell carcinoma, as this is the first time an immunotherapy treatment option has been approved in the European Union for this patient population,” said Ian M. Waxman, MD, development lead, gastrointestinal cancers, Bristol Myers Squibb, in the press release. “We are proud of our work in advancing treatment options for people living with upper gastrointestinal cancers, and we look forward to working with European stakeholders to bring Opdivo to more eligible patients who may benefit.”

In addition to this approval in the European Union, Opdivo has been approved in five countries, including the United States and Japan, for the second-line treatment of patients with unresectable advanced, recurrent or metastatic ESCC.

The EC’s approval was based on positive results from a Phase III clinical trial that demonstrated a statistically significant and clinically meaningful improvement in patients compared to chemotherapy.

EC Approves Bristol Myers Squibb’s Opdivo in Second-Line Treatment of Esophageal Cancer

On Nov. 23, 2020, biopharmaceutical company CureVac and contract development and manufacturing organization Wacker Chemie jointly announced that they have signed a contract for the manufacture of CureVac’s COVID-19 mRNA-based vaccine candidate, CVnCoV. Under terms of the initial agreement, Wacker will ramp up good manufacturing practice (GMP) production of the mRNA drug substance for the vaccine at its biotech site in Amsterdam in the first half of 2021.

Preparations for the start of production, technology transfers, and test runs are already underway, the companies reported in a press release. Wacker plans to produce more than 100 million doses of the CureVac vaccine per year at its Amsterdam site. The site can also be further expanded to meet rising demand in the future.

The Amsterdam site has a history of producing vaccines for clinical development and commercial supply, with a portfolio that ranges from conventional live and killed vaccines to protein-based, polysaccharide and glycoconjugate vaccines. Wacker has invested in the site in recent months to extend production to include mRNA-based vaccines.

Wacker will support production of CureVac’s COVID-19 mRNA-based vaccine candidate at its biotech site in Amsterdam, with production scheduled to start in the first half of 2021.

CureVac and Wacker Sign Manufacturing Contract for COVID-19 Vaccine Candidate

Dolomite Microfluidics, a UK-based microfluidic solutions provider, has partnered with MilliporeSigma to create a range of off-the-shelf NanoFabTx microfluidic device kits that can produce poly (lactic-co-glycolic acid) (PLGA) nano- and microparticles for drug development and controlled drug release applications. The kits (available exclusively from MilliporeSigma) can also be applied to the encapsulation of drugs and other therapeutics in liposomes, such as the SARS-CoV-2 (COVID-19) vaccines currently under investigation.

The increasing use of biodegradable PLGA polymers for drug encapsulation and formulation of controlled release preparations has created a market for easy-to-use, ready-to-go microfluidic solutions. These solutions simplify the workflow for researchers, Dolomite stated in a Nov. 10, 2020 press release.

The new NanoFabTx kits include a microfluidic chip, holders, and accessories, along with application data for the production of a variety of particle types and sizes. To use the kit, simply connect it to the pumps and start the application, Dolomite noted in its press release. This microfluidic approach is user-friendly and offers better encapsulation efficiency and higher monodispersity than traditional methods.

The kit offers the benefit of particle isolation (for particles of the correct dimensions) without wasteful filtering, which ensures the tight control of particle size and shape that is essential to regulating the speed of drug delivery and release. The new kits are intended for use with MilliporeSigma’s NanoFabTx PLGA-Nano and NanoFabTx PLGA-Micro Reagent kits and are optimized for microfluidic pumps and software from Dolomite, to give high accuracy and consistency. The kits can also be combined with Dolomite’s high throughput Telos technology for scaled up experiments.

“MilliporeSigma chose Dolomite Microfluidics because of our reputation and many years’ expertise in providing excellent microfluidic solutions that deliver consistent and reliable production of particles. The controllability and reproducibility that microfluidics offers means the process is really finding its place in drug and vaccine development, making it the method of choice. We are looking forward to continuing our work with scientists to keep getting particles out there at the forefront of this area,” said Richard Gray, commercial director at Dolomite Microfluidics, in the press release.

Dolomite Microfluidics and MilliporeSigma have begun a collaboration to release off-the-shelf microfluidic device kits for the fabrication of PLGA particles.

Dolomite Microfluidics Partners with MilliporeSigma for Microfluidic Device Kits 

The recent commercial launch in November 2020 of a new, small, portable microplate reader by Enzo Biochem, a US-based biosciences and diagnostics company, is expected to simplify laboratory workflows. The new microplate reader can be used with Enzo’s immunoassays and, ultimately, molecular diagnostics, providing new opportunities in point-of-care medicine.

The advanced design and technology of the compact microplate reader makes it possible to deliver precise and accurate results. Used together with Enzo’s proprietary software, the device can be used in a wide variety of applications based on the miniaturization of Enzo’s assays, including metabolites, hormones (e.g., pregnancy), proteins (e.g., inflammatory cytokines), and protein characterization.

The instrument provides researchers and lab professionals with a dedicated, personal device to conveniently fit their space and needs and offers accessibility not previously available. The handheld instrument is about one-tenth the size of the average benchtop plate reader, allowing it to fit into any laboratory setting and saving bench space. At the same time, the device provides new levels of flexibility and portability that can be extended to point-of-care facilities, allowing physicians to provide molecular testing, including assays for viral detection and sexually transmitted diseases.

With this new technology, point-of-care testing can move from centralized, complex clinical labs closer to patient care, Enzo stated in a Nov. 5, 2020 company press release. The technology simplifies testing procedures and opens up the opportunity to shift testing out of the hands of licensed medical technicians to healthcare professionals operating nearer to patients or, in some instances, even to patients themselves.

“Access to point-of-care testing continues to grow as technological advances in clinical diagnostic testing drive miniaturization of complex devices. Now, just as computers moved from mainframes to powerful, portable handheld devices, the same is happening within the clinical diagnostic testing industry. This reduced complexity provides high quality and precise testing capabilities to be available to a broader range of healthcare professionals involved in patient management whether they are sitting at an urgent care facility, a doctor’s office or hospital bedside,” said Kara Cannon, chief commercial officer of Enzo, in the press release.

“The point-of-care testing market, currently valued at over $18 [billion] globally, has the potential to aggressively expand to many testing needs that are now not widely available at point-of-care, including a significant portion of the $15 [billion] immunoassay testing market,” Cannon added. “Common clinical immunoassay tests, such as vitamin D testing and inflammation analysis, currently are performed regularly in the clinical central testing lab by licensed medical technologists using large, complex instrumentation. Unlike lateral flow assays, this small yet powerful system does not sacrifice sensitivity for convenience and allows for multi-assay capabilities.”

“Enzo’s corporate vision addresses new opportunities for expansion and growth within both products and services,” said Cannon in the press release. “We are serving markets including laboratories, point-of-care, and direct-to-consumer. This market launch is an important step in extending our offerings beyond the central laboratory, enabling physicians to provide clinical testing at their office, urgent care facility, or other treatment center.”

Enzo anticipates a future launch of isothermal testing on this same platform, enabling constant temperature and eliminating the need for a thermal cycler.

The new powerful, precise, and compact instrument can be retrofitted for point-of-care clinical testing at urgent care facilities, hospitals, or physicians’ offices.

Enzo’s New Portable Microplate Reader Simplifies Laboratory Workflow

In selecting Domainex, a UK-based biotechnology company specializing in integrated medicines research, to provide integrated lead optimization services, APEIRON Biologics, a privately held Austrian biotech company focused on cancer and respiratory therapies, will be able to advance the development of inhibitors for the E3 ubiquitin ligase Cbl-b using small-molecule drug discovery.

Under this agreement, Domainex will provide its expertise in medicinal and computational chemistry, screening, structural biology, and absorption, distribution, metabolism, excretion, and pharmacokinetics (ADME/PK) to advance APEIRON’s Cbl-b targeting compound series, APN431, towards pre-clinical development.

To date, Domainex has provided APEIRON with its expertise in hit identification, both fragment-based and virtual screening, by establishing and deploying a suite of biophysical assays against variants of the E3 ligase Cbl-b and other members of this target class. These assays allowed the companies to determine the binding affinity, mechanism, and selectivity of promising compounds.

With the expanded deal, the partnership will progress into the next stage, under which Domainex will provide lead optimization services.

“We are delighted to move into this new phase of our partnership with APEIRON Biologics to support the discovery and development of new medicines to treat cancer. Our multi-disciplinary team of scientists has been successful at generating multiple compound series with promising properties. Their commitment through seven-day a week operations and implementation of shift-patterns has enabled us to continue to progress client-sponsored projects throughout the COVID-19 pandemic whilst maintaining social distancing at our state-of the art Medicines Research Centre. We look forward to continuing our journey of discovery with APEIRON,” said Dr. Tom Mander, CEO of Domainex, in a Nov. 9, 2020 company press release.

“Finding the right research partner for the development of our highly innovative immune-oncology therapeutics is essential for fast, efficient, and ultimately successful results. We are delighted to expand our partnership with Domainex for our Cbl-b targeted APN431 project and help us to quickly move to the next stage of its development. Domainex provides deep know-how in state-of-the-art structure based medicinal chemistry and assay development to help us achieve our ambitious goals. With our small-molecule program, APN431, we have an additional approach to target Cbl-b, next to our autologous cell therapy program, APN401, which is currently in clinical Phase I development,” said Peter Llewellyn-Davies, CEO of APEIRON Biologics, in the press release.

The expansion of the companies’ partnership will integrate lead optimization efforts to advance cancer immune therapy drug discovery.

Expansion of APEIRON Biologics and Domainex Partnership will Advance Cancer Drug Discovery

Merck, known as MSD outside the United States and Canada, and OncoImmune, a US-based clinical-stage biopharmaceutical company, announced on Nov. 23, 2020 that they have entered into an acquisition agreement where Merck will acquire all outstanding shares of OncoImmune for an upfront payment of $425 million in cash.

Under the terms of the agreement, Merck will fast-track the development of OncoImmune’s COVID-19 therapeutic candidate, CD24Fc, a first-in-class recombinant fusion protein that targets the innate immune system, currently in Phase III clinical development for the treatment of severe and critical disease patients. The therapeutic candidate recently received positive results from an interim efficacy analysis of data from the Phase III study.

“Meaningful new therapeutic options are desperately needed for possibly millions of people around the world who will develop severe or critical COVID-19 disease,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories, in a company press release. “Recent clinical investigations support the view that CD24Fc may provide benefit beyond standard-of-care therapy for COVID-19 patients requiring oxygen support, and hence will represent an important addition to the Merck pipeline of investigational medicines and vaccines designed to address the COVID-19 pandemic.”

“Outstanding work by the OncoImmune team has provided compelling evidence regarding the use of CD24Fc in patients with severe and critical COVID-19 in our Phase III trial,” added Yang Liu, PhD, co-founder and CEO of OncoImmune, in the press release. “We look forward to working with the scientists and manufacturing engineers at Merck as well as regulators as we seek to accelerate the global development of this potentially important therapy.”

The acquisition gives Merck a new Phase III COVID-19 therapeutic candidate, CD24Fc, a fusion protein that targets the innate immune system, in its pipeline.

Merck to Acquire OncoImmune for $425 Million

Mustang Bio, a US-based clinical-stage biopharmaceutical company, and Minaris Regenerative Medicine, a cell and gene therapy contract development and manufacturing organization, announced on Nov. 23, 2020 that they have entered into an agreement for the technology transfer and clinical manufacturing of Mustang’s MB-107 lentiviral gene therapy program for the treatment of X-linked severe combined immunodeficiency (XSCID), also known as bubble boy disease, in Europe.

Through the agreement, Minaris will initiate the technology transfer of the manufacturing and analytical processes and will integrate it into the European regulatory environment for manufacturing at its Ottobrunn, Germany site in order to supply clinical trials in Europe, a Mustang press release said.

“We look forward to a productive and successful partnership with Mustang where Minaris will be able to support them with our extensive experience in the clinical and commercial manufacturing of autologous gene therapies,” said Dusan Kosijer, managing director of Minaris, in the press release. “We are eager to work together with Mustang in the fight against this devastating disease.”

“This agreement with Minaris is an important step in supporting expansion of our MB-107 pivotal clinical trial into Europe,” said Manuel Litchman, MD, president and CEO of Mustang, in the press release. “We look forward to working with Minaris to grow our geographic footprint and bring this potential life-saving therapy to XSCID patients in need internationally.”

The companies have entered into an agreement for the technology transfer and clinical manufacturing of Mustang’s MB-107 lentiviral gene therapy program for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, in Europe.

Mustang Bio to Enter into Agreement with Minaris Regenerative Medicine for Gene Therapy Manufacturing in Europe

Baxter announced on Nov. 24, 2020 that it is investing $50 million into the expansion of its sterile fill/finish manufacturing facilities in Bloomington, IN.

The expansion will include a new 25,000 ft-

 warehouse, a filling line for flexible plastic containers, a high-speed automated syringe fill line with the ability to fill up to 600 units per minute, and a high-speed automated visual inspection line, a company press release said. Construction is expected to be completed in 2021, and the new facilities will create 100 new jobs at the site.

“We pride ourselves on being a contract manufacturing partner with the specialized expertise, proven experience, and facilities to help our clients successfully achieve their sterile manufacturing objectives,” said Marie Keeley, vice-president, BioPharma Solutions, Baxter, in the press release. “Our Bloomington facility is already a global leader in sterile contract manufacturing, and this expansion will add capacity and state-of-the-art technology that will better enable us to meet the diverse needs of our clients and the patients they serve.”

The expansion will include a new 25,000-ft2 warehouse, a filling line for flexible plastic containers, a high-speed automated syringe fill line with the ability to fill up to 600 units per minute, and a high-speed automated visual inspection line.

Baxter to Invest $50 Million into Indiana Fill/Finish Manufacturing Facilities Expansion

Sanofi announced on Nov. 23, 2020 that the European Commission (EC) approved MenQuadfi (meningococcal [groups A, C, Y, W] conjugate vaccine) for immunization against meningococcal meningitis, the inflammation of the brain and spinal cord caused by a viral infection, in patients from the age of 12 months and older.

The EC’s approval comes after positive results from seven Phase II and III randomized, active-controlled, multi-center studies, a Sanofi press release said. Immunogenicity and safety of the vaccine were assessed in 6300 individuals who received a single dose of MenQuadfi, which showed a good safety profile and induced a high immune response against all four 

“Meningococcal meningitis can take one’s life in as little as one day and leave survivors with severe permanent disabilities. In Europe, there were more than 3000 cases of Invasive Meningococcal Disease in 2018, half of them caused by serogroups C, W, and Y,” said Thomas Triomphe, head of Sanofi Pasteur, in the press release. “One case is one too many. It is our ambition to make this vaccine available worldwide to further expand protection to as many people as possible. The European Commission’s approval of MenQuadfi takes us one step closer to achieving this goal.”

The EC’s approval comes after positive results from seven Phase II and III randomized, active-controlled, multi-center studies.

Featured Content

Unique Molecules Push Formulation Boundaries

COVID-19 Therapy Developments