Drug Solutions Podcast

Data analytics, modular equipment, digital tools, and risk-based validation improve speed, flexibility, and quality.

Streamlining Equipment Quality and Flexibility

Opportunities and developments in particle engineering are providing developers with the tools to advance drug candidates successfully.

Putting a Spotlight on Particle Engineering

Advancements in soft capsule technology can enable the development of soft capsule formulations.

Novel Formulations and Line Extensions with Soft Capsule Technology

Examining new approaches, novel technologies, and the structural evolution of the raw materials market.

Examining Trends in Oral Solid Dosage Manufacturing

Replacing a step in sample preparation with an automated approach improves both method precision and productivity.

Automating a Critical Step in Glycoprotein Analysis for Vaccine Manufacture

Advancing OSD: Continuous Production Considerations and Dose-Level Authentication

Drug Digest

MillporeSigma announced on Nov. 16, 2022 that its life science business sector is investing more than $286 million in its biosafety testing capacity at the company’s site in Rockville, Maryland. A new, state-of-the-art, 250,000 ft2 facility at the site will house biosafety testing, analytical development, viral clearance suites, and cell bank manufacturing services.

According to a company press release, the goal of this investment is to significantly increase the company’s ability to conduct biosafety testing and analytical development services. Over the next four years, the company expects the expansion to create more than 500 new jobs.

“MilliporeSigma is harnessing its broad portfolio of modern technologies and enabling services to help ensure the safety of the world’s medicines. These significant investments in Rockville and other sites across our global network will help us meet growing demand for the robust testing studies that biologics manufacturers depend upon to comply with stringent regulatory guidelines,” said Belén Garijo, chair of the executive board and CEO, Merck KGaA, Darmstadt, Germany, in the release. “This is a prime example of our focus on sustainable growth in areas with strong underlying upwards dynamics.”

“This is the largest investment in contract testing in Merck KGaA, Darmstadt, Germany’s history,” said Matthias Heinzel, member of the executive board, Merck KGaA, Darmstadt, Germany, and CEO, Life Science. “We thank the State of Maryland and Montgomery County, Maryland, for their collaboration in making this new campus a reality for our employees and clients. Together, we are impacting life and health with science.”

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The $286 million investment ability is designed to elevate MillioporeSigma’s ability to conduct biosafety testing and analytical development services.

MilliporeSigma Invests $286 Million in US Drug Safety Testing Capacity

Regeneron and CytomX Therapeutics, a clinical-stage biopharmaceutical company focused on oncology, announced a collaboration and licensing agreement on Nov. 17, 2022. The collaboration will see the companies partner to develop investigational next-generation bispecific immunotherapies for cancer using CtyomX’s Probody therapeutic platform and Regeneron’s Veloci-Bi bispecific antibody development platform.

According to a company press release, the agreement will see Regeneron and CytomX collaborate on the discovery activities to identify and validate conditionally active bispecific antibodies. Regeneron will be responsible for funding preclinical and clinical development and commercialization activities. CytomX will receive a $30 million upfront payment with the potential for up to $2 billion in research, development, regulatory, and sales-based milestones, as well as tiered global net sales royalties.

The partnership intends to use CytomX’s biologic masking strategies to develop investigational Regeneron bispecifics that remain inactive until activated by proteases in the tumor microenvironment. According to the release, this technology would have the potential to widen the therapeutic window and help minimize off-target effects for next-generation T-cell engaging therapies, allowing them to potentially address tumor types typically unresponsive to immunotherapy.

"At Regeneron, we're focused on developing a paradigm-changing portfolio of oncology medicines for patients, by combining a deep understanding of cancer biology with cutting-edge technologies," said John Lin, senior vice-president of Immuno-oncology, head of Bispecifics, Regeneron, in the release. "This collaboration will enable Regeneron and CytomX to combine our collective oncology expertise with two premier platforms – Probody and Veloci-Bi – to develop novel immunotherapies and research their potential to transform patient lives."

"CytomX has pioneered the field of conditionally-activated therapeutics through high quality and differentiated science, leading to broad experience in biologic masking strategies and a deep understanding of the protease tumor microenvironment," said Sean McCarthy, CEO and chairman, CytomX, in the release. "We are thrilled that our scientific expertise has attracted Regeneron as our newest collaborator, and we look forward to working closely together to further optimize T-cell engager strategies and push the boundaries of cancer immunotherapy to new levels."

The collaboration will see the companies develop investigational next-generation bispecific immunotherapies for cancer.

Regeneron and Cytomx Announce $2 Billion Oncology Collaboration

In November 2022, Bio-Rad Laboratories launched its Pioneer Antibody Discovery Platform, a new antibody discovery service specifically designed to develop best-in-class biologic candidates.

According to a Nov. 14, 2022 company press release, the Pioneer platform has an enhanced phage display library that includes more than 200 billion unique sequences. Additionally, the platform is capable of identifying high-affinity antibody candidates via Bio-Rad’s SpyDisplay selection technology. The technology is optimized for candidates suitable for drug development.

The platform is tailored to specific client requirements and uses proprietary TrailBlazer technology to provide prototypes of therapeutic antibodies in various formats for streamlined lead identification. Final immunoglobulin g antibodies are delivered functionally characterized with a complete data package and sequences. Customers retain exclusivity and ownership over antibody sequences produced from the platform.

"The commercial launch of Pioneer Platform demonstrates Bio-Rad's focus on supporting the biotherapeutic space," said John Cardone, marketing manager, Custom Antibodies, Life Science Group, Bio-Rad, in the release. "With decades of experience in antibody discovery, our team of scientists and technical specialists accelerate and simplify the process to identify functional biologics for the targets of interest."

The Pioneer Antibody Discovery Platform is a new antibody discovery service specifically designed to develop best-in-class biologic candidates.

Bio-Rad Introduces Pioneer Antibody Discovery Platform for Therapeutic Development

FDA announced the approval of Provention Bio’s Tzield (teplizumab-mzwv) injection as a treatment for type 1 diabetes on Nov. 17, 2022. Teplizumab-mzwv is the first FDA-approved therapy designed to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older.

According to an agency press release, teplizumab-mzwv binds to certain immune system cells and delays the progression to stage 3 type 1 diabetes. It is designed to deactivate the immune cells that attack insulin-producing cells, increasing the proportion of cells that help moderate the immune response. The treatment is administered via intravenous infusion once daily over 14 consecutive days.

FDA based its approval on a randomized, double-blind, event-driven, placebo-controlled trial featuring 76 patients with stage 2 type 1 diabetes. Patients received either teplizumab-mzwv or a placebo once daily via intravenous infusion for 14 days. The primary efficacy measure was the time from randomization to the development of stage 3 type 1 diabetes. Of the patients who received teplizumab-mzwv, 45% were diagnosed with the condition over a median follow-up of 51 months versus 72% of those who received a placebo. Additionally, the mid-range time from randomization to stage 3 type 1 diabetes diagnosis was 50 months for the patients who received teplizumab-mzwv versus 25 months for those who received a placebo.

“Today’s approval of a first-in-class therapy adds an important new treatment option for certain at-risk patients,” said John Sharretts, director of the Division of Diabetes, Lipid Disorders, and Obesity, FDA’s Center for Drug Evaluation and Research, in the release. “The drug’s potential to delay clinical diagnosis of type 1 diabetes may provide patients with months to years without the burdens of disease.”

Tzield (teplizumab-mzwv) injection is the first FDA-approved therapy designed to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older.

FDA Approves Injection Designed to Delay Onset of Type 1 Diabetes

Ardelyx, a biopharmaceutical company focusing on medicines that meet significant unmet medical needs, announced positive findings from FDA’s Cardiovascular and Renal Drugs Advisory Committee (CRDAC) meeting concerning XPHOZAH (tenapanor) on Nov. 16, 2022. While it was once rejected by FDA, the panel voted for its approval as a treatment for the control of serum phosphorus in adult patients with chronic kidney disease on dialysis. It received a majority vote as both a monotherapy and combination treatment with phosphate binder.

According to a company press release, tenapanor is an investigational first-in-class phosphate absorption inhibitor with a unique blocking mechanism of action, which acts locally in the gut to inhibit the sodium hydrogen exchanger 3. This reduces phosphate absorption through the paracellular pathway, the primary pathway of phosphate absorption, allowing for control of serum phosphorus in the patient's blood. The drug is taken as a 30 mg tablet twice daily.

CRDAC based its decision on findings concerning tenapanor on a comprehensive development program that included more than 1,200 patients in three Phase III clinical trials that evaluated its safety and efficacy. According to the release, all the trials met their primary and key secondary endpoints.

"Today's vote by the CRDAC is a promising development for the chronic kidney disease community, as patients continue to struggle to control serum phosphorus levels despite [the] use of currently available therapies, which are all limited to the phosphate binder class," said Mike Raab, president and CEO, Ardelyx, in the release. "We are hopeful following today's discussion that the data, the opinion of the advisory committee, the needs of patients, and the compelling voice of the broader nephrology community will be reflected in the FDA's decision on our appeal."

"[Tenapanor] is a novel treatment that provides a clinically meaningful effect on serum phosphate,” said Sharon Moe, chief of the division of nephrology and hypertension at Indiana University School of Medicine, in the release. I am encouraged by the committee's vote. The nephrology community is enthusiastic to have access to this therapy with its novel mechanism of action to help our patients."

While CRDAC’s recommendations are not binding, they will be considered by FDA’s Office of New Drugs (OND) when making its decision on Ardelyx’s appeal for tenapanor. OND is expected to provide a response to the appeal within thirty days.

Initially rejected in July 2021, XPHOZAH (tenapanor) won recommendations as both a monotherapy and combination treatment from FDA’s CRDAC meeting.

FDA Committee Recommends Ardelyx Kidney Disease Drug 

Cradle, a platform company that helps scientists design and program proteins, has launched from stealth with €5.5 million (US$5.4 million) in seed funding, with a synthetic biology platform that uses artificial intelligence to design protein machines and cell factories.

Cradle’s technology gives scientists the ability to reverse engineer proteins with the desired specific properties. The company has built a working synthetic biology platform that is already in use by a number of early-stage design partners. For example, a biologist may want to change a protein to guarantee its stability at a certain temperature so that the protein will attach to a specific chemical in its vicinity. Cradle’s technology—which entails self-teaching, self-improving generative machine learning models that draw on recent advances in natural language processing—can predict which parts of a protein’s genetic code a biologist will need to alter. This advantage can significantly improve a scientist’s chances of getting the experimental results they want, according to a Nov. 17, 2022 company press release.

The Cradle platform further improves the performance of these large-molecule models on specific tasks within the context of biological research. The company also offers an intuitive and collaborative online platform to make these models accessible to scientists without a machine learning background. This method can conceivably reduce the time and cost of getting a synthetic biology product to market by an order of magnitude, according to the company press release.

“You can think of cells like tiny factories, with proteins as the assembly lines and machines that allow them to make different end-products. With the right tweaks, we can make proteins that will make all manner of new products far more efficiently and with a much lower environmental impact,” said Stef van Grieken, Cradle’s CEO and co-founder, in the press release. “With current methods, a biologist can spend years trying to find the right solution to any particular problem. By harnessing the power of machine learning, our platform can substantially speed up the design, build, and scaling phases when bioengineering proteins, making it possible to create and scale synthetic biology projects much faster and more cost-effectively. Our goal is to reduce the cost and time of getting a bio-based product to market by an order of magnitude so that anyone—even 'two kids in their garage'—can bring a bio-based product to market.”

The seed funding the company has obtained will be used to accelerate product development, build out the company’s offering, scale its team, and support the onboarding of more design partners. The funding was co-led by Index Ventures and Kindred Capital. Leading angel investors who also participated in the financing round include Feike Sijbesma, honorary chairman and former CEO of Royal DSM, and Emily Leproust, founder of Twist Bioscience.

Biotech startup, Cradle, has raised $5.4 million in seed funding with an AI-enabled design platform that allows for the synthetic building of cell factories to produce proteins.

Biotech Startup Raises $5.4M to Develop AI-Designed Protein Machines and Cell Factories

In November 2022, Element Materials Technology, a global testing, inspection, and certification company, unveiled its newest bioaerosol testing facility at its Eagan, Minn., site. The facility is designed to evaluate the efficacy of aerosolized products to reduce or eliminate indoor airborne organisms and viral particles in habitable spaces (e.g., transportation, hospitals, and schools). According to a Nov. 16, 2022 company press release, the facility is one of the first and largest post-pandemic, commercial bioaerosol testing facilities.

 Eagan facility offers real-world modeling of habitable spaces, such as hospitals, schools, and other large spaces, and houses a biocontainment lab that can be used in dual or single capacity, which allows for simultaneous testing of control and treated space under the same conditions. The lab also offers various size configurations, including 107 m

, among other sizes. In addition, the lab can manage multiple air-handling scenarios, including the introduction of fresh or recirculated air. It has the capacity to test biosafety level 2 organisms, including mammalian viruses.

Because the US Environmental Protection Agency (EPA) is aiming to release guidance for air treatments in 2022 or early 2023, Element has played an instrumental role in developing a standard test method for EPA-approved public health claims for air treatments, according to the company press release. Element is collaborating with regulatory, academic, and industry experts on developing these standard test methods.

“The need for bioaerosols was defined by the pandemic, and Element is pleased to bring the industry this new, much-needed capability to fulfill emerging and critical testing needs. Precise and accurate air quality testing will be critical for public health for the future,” said Elisabeth Lackner, chief scientific officer of Element, in the press release. “We are helping customers to establish purposefully designed bioaerosol R&D level protocols that provide a strong foundation for future GLP [good laboratory practice]-compliant testing.”

Element has opened a new 7500-ft3 facility that will be used to evaluate aerosolized product efficacy for reducing airborne organisms and viral particles.

Element’s New Air Treatment Testing Facility Supports Indoor Space Public Health Air Quality

On Nov. 16, 2022, Theragent, a newly emerged, US-based cell therapy contract development and manufacturing organization (CDMO), announced that CellVax Therapeutics, a French late-stage clinical-trial company, selected it to provide manufacturing and testing services for CellVax’s novel cancer immunotherapy candidate, FK-PC101. FK-PC101 is entering Phase II clinical trials.

The immunotherapy candidate is a cell based autologous cancer vaccine for prostate cancer. It is intended for patients who have a high risk of recurrence after prostatectomy. Under the agreement, the two companies have begun preparations for the manufacturing partnership, including project planning and analytical method tech transfer. Manufacturing services will start in late 2022. Theragent has agreed to supply autologous cell-derived doses to support CellVax’s early and pivotal trials in the United States.

“Theragent is a newer CDMO, but we have assembled a team that brings decades of experience in the development and production of autologous cell-based products around the world,” said Jeff Masten, chief operating officer, Theragent, in a company press release. “We are thrilled to support CellVax and their promising Phase [II] cancer vaccine candidate. Not only does this project fit seamlessly into our new … [C]GMP [current good manufacturing practice] manufacturing facility in Southern California, but the incredible science behind FK-PC101 is a harmonious fit with our company mission of delivering advanced medicines to cancer patients in need.”

“With our proprietary immunotherapy platform, we modify the patient’s tumor cells 

, inducing them to behave as antigen-presenting cells, which are then formulated into a personalized cancer vaccine for that individual. We look forward to partnering with Theragent on the further development of this truly novel modality,” said Fernando Kreutz, CEO of CellVax, in the press release.

CellVax Therapeutics has selected Theragent, a new CDMO, to manufacture clinical trial material for a new Phase II prostate cancer immunotherapy drug candidate.

CellVax and Theragent Form Manufacturing Pact for Novel Cancer Immunotherapy Drug Candidate

Sanofi and Insilico Medicine, a clinical-stage biotechnology company, announced a multi-year strategic research collaboration on Nov. 8, 2022. The agreement will see Sanofi use Insilico’s AI platform, Pharma.AI, to advance drug development in up to six new targets.

According to a company press release, Sanofi will pay $21.5 million in upfront and target nomination fees. Additional payments for various research, development, and sales milestones reach as high as $1.2 billion, as well as mid-single to low double-digit tiered royalties for any products developed.

“We look forward to working with Insilico Medicine, a demonstrated leader in AI-powered drug discovery,” said Changchun Xiao, head of China Research, Sanofi, in the release.“This collaboration will leverage our complementary capabilities, as well as the co-location of our scientific teams, to boost the drug discovery efforts of the Sanofi Institute for Biomedical Research (SIBR), Sanofi’s R&D center in China.”

“We are very happy to collaborate with Sanofi, a company with a clear strategy in AI-powered drug discovery,” said Alex Zhavoronkov, CEO and founder, Insilico Medicine, in the release. “This close collaboration will allow Sanofi to immediately gain the capabilities of one of the top AI startups in addition to enriching their drug discovery pipeline."

The deal will see Sanofi use Insilico’s AI drug discovery platform to advance up to six new drug development candidates.

Sanofi and Insilico Medicine Ink $1.2 Billion Drug Development Deal

Indiviaor, a pharmaceutical company focused on treatments for addiction and serious mental illnesses, announced its acquisition of Opiant Pharmaceuticals, a company developing treatments for addiction and drug overdose, for approximately $145 million on Nov. 12, 2022. This acquisition grants Indivior the rights to OPNT003, an investigational opioid overdose reversal agent, as well as other treatments in their pipeline.

According to a company press release, OPNT003 is an intranasal nalmefene formulation that utilizes an absorption-enhancing technology (Intravail) to enhance its pharmacodynamic profile, allowing it to act more quickly and relative to certain naloxone-based rescue agents such as NARCAN Nasal Spray. OPNT003 received fast track designation from FDA in November 2021 and Opiant is expected to complete its new drug application submission in the fourth quarter of 2022. Should it receive FDA approval, anticipated approval for a fast-track application is third quarter 2023, with launch in the United States expected in the ensuing months.

"Our work in combating addiction has never been more critical, with overdose deaths in the US occurring at near record numbers,” said Mark Crossley, CEO, Indivior, in the release. “Opiant’s portfolio of product candidates is an excellent strategic fit that diversifies and strengthens our offerings, while Indivior’s strong commercial capabilities are expected to propel a combined product pipeline with the potential to help patients along a continuum from substance use disorder and rescue to recovery.”

“We are pleased to have reached an agreement that reflects the great potential Opiant has created with OPNT003 and our pipeline of medicines,” said Roger Crystal, president and CEO, Opiant, in the release. “This transaction combines Opiant with an organization that shares our patient-focused mindset, and we believe creates immediate value for patients, our employees, and our stockholders. It will enable us to leverage Indivior’s global scale, commercial strength, and scientific expertise to accelerate our mission to create best-in-class medicines for the treatment of substance use disorders and drug overdose.”

In addition to OPNT003, two other key treatments are in Opiant’s pipeline, PONT002 and OPNt004. OPNT002, or nasal naltrexone, is currently in a Phase II trial to assess its potential as a treatment for alcohol drinking and cravings. OPNT004 is a cannabinoid receptor type 1 antagonist in preclinical development as a potential injectable treatment for acute cannabinoid overdose.

Indivior’s acquisition of Opiant grants them access to the company’s portfolio of investigational opioid overdose reversal agent, OPNT003.