Practical and operational considerations related to paediatric oral drug formulation: An industry survey

For over 15 years, US and EU regulations have ensured that medicines developed for children are explicitly authorised for such use with age-appropriate forms and formulations, implying dedicated research.

To shed light on how these regulations have been adopted by pharmaceutical companies and how various aspects of paediatric oral drug formulation development are currently handled, an exploratory survey was conducted. Topics included: general company policy, regulatory aspects, dosage form selection, in-vitro, in-silico and (non-)clinical in-vivo methods, and food effects assessment. The survey results clearly underline the positive impact of the paediatric regulations and their overall uptake across the pharmaceutical industry.

Even though significant improvements have been made in paediatric product development, major challenges remain. In this respect, dosage form selection faces a discrepancy between the youngest age groups (liquid products preference) and older subpopulations (adult formulation preference). Additionally, concerted research is needed in the development and validation of in-vitro tools and physiology-based pharmacokinetic models tailored to the paediatric population, and in estimating the effect of non-standard and paediatric-relevant foods.

The current momentum in paediatric drug development and research should allow for an evolution in standardised methodology and guidance to develop paediatric formulations, which would benefit the pharmaceutical industry and regulators.

Read the article featured in International Journal of Pharmaceutics

"The pharmaceutical industry is being revolutionised by the utilisation of digital technologies. Chemistry 4.0 describes this digital transformation and how its delivery is paving the way for the industry’s next stage of development."

This article explores the range of digital technologies which are now being employed across the drug development pathway. Quotient's Sr. Director of Science & Technology, Gareth Jenkins, and Head of Drug Substance, Paul Quigley, share their insights on Chemistry 4.0 and the digital transformation of the pharmaceutical industry.

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Evecxia Therapeutics Reports Favorable Data From a Phase 1 Single-Ascending Dose and Multiple-Ascending Dose Trial of Adjunctive EVX-101 in Healthy Volunteers Treated With a First-Line Antidepressant

The Phase 1 trial of EVX-101 in healthy volunteers was conducted at Quotient Sciences - Nottingham.

April 10, 2023 - Evecxia Therapeutics, Inc. announced favorable safety, tolerability, pharmacokinetic, and pharmacodynamic data from a double-blind, placebo-controlled Phase 1, a two-part single ascending dose (SAD) and multiple ascending dose (MAD) trial of EVX-101 in healthy volunteers treated with escitalopram. The Company further announced the planned design of a Phase 2 adjunctive EVX-101 trial in patients with major depressive disorder (MDD) responding inadequately to a first-line antidepressant (selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI)).

EVX-101 is a novel, proprietary gastro-retentive, sustained-release tablet formulation of 5-hydroxytryptophan (5-HTP), the natural precursor to serotonin, and low-dose carbidopa. EVX-101, administered in addition to a first-line antidepressant, is intended to elevate extracellular serotonin beyond the first-line antidepressant effect, which convergent clinical pharmacology, brain imaging, and neuroanatomical data support would augment antidepressant efficacy. In EVX-101, the 5-HTP dose is fixed at 250 mg, while variable levels of carbidopa control 5-HTP plasma exposure levels.

The Phase 1 trial was conducted at Quotient Sciences’ Nottingham, UK facility.

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Collaboration Expedites Human Clinical Trials for COVID-19 Drug Candidate

NOTTINGHAM, U.K., and PITTSBURGH, April 28, 2020 – A collaboration to accelerate the development of a lead COVID-19 drug candidate into human clinical trials was announced today by Quotient Sciences, a leading provider of innovative drug development and manufacturing solutions, and CytoAgents, Inc., a privately held biotechnology company focused on the development of pharmaceutical products for the treatment of viral infectious diseases. The partnership will focus on utilizing Quotient Sciences' integrated service portfolio to support the rapid development of CytoAgents’ lead COVID-19 drug candidate, GP1681, for Phase I and II in 2020.

Scientific consensus is building that severe illness caused by COVID-19 and other infectious diseases is triggered by a phenomenon known as “cytokine storm,” an excessive immune response that attacks the body. GP1681 is a small molecule inhibitor of cytokine release in activated human immune cells and has been shown to safely modulate the natural immune response by tamping down various cytokines. GP1681 addresses an unmet need for therapeutic treatment by targeting the underlying cause of life-threatening symptoms associated with cytokine storm, which can cause more harm than the virus itself.

“Our mission is to create a powerful, lasting solution, not just for the current crisis but for any respiratory epidemic, thereby saving lives and reducing the strain on healthcare facilities,” said Teresa Whalen, RPh, CEO, CytoAgents. “Working with Quotient Sciences is a major milestone for CytoAgents in its accelerated path for a universal treatment for COVID-19-related or any respiratory epidemic.”

Mark Egerton, Ph.D., CEO of Quotient Sciences, said, “The COVID-19 pandemic has caught humanity off guard, and we need to act swiftly to bring new medicines to patients around the world. We are delighted to support CytoAgents with the product development of GP1681.”

Under the scope of the agreement, CytoAgents will access Quotient Sciences' formulation and manufacturing expertise to develop and rapidly supply drug product for Phase I and II testing in 2020. In parallel, Quotient Sciences will work to develop a scalable solid oral dosage form for larger patient trials and commercialization. The program will be conducted at Quotient’s facility in Garnet Valley, PA, which has specialized drug handling and containment suitable for highly potent drug candidates.

About Quotient Sciences

Quotient Sciences is an innovative global pharmaceutical development, clinical, and commercial manufacturing organization providing services to the pharmaceutical and biotech industries. A combination of specialized skills and agile integrated processes enables Quotient Sciences to develop customized solutions that dramatically reduce the time and cost of getting drugs to market. Everything we do is driven by a deeply held belief, shared across the entire organization, that molecules need to become cures — fast.

About CytoAgents

CytoAgents is a privately held biotechnology company focused on the development of innovative pharmaceutical products for the treatment of COVID-19, influenza, viral infectious diseases and conditions that cause acute respiratory distress. Using a novel, host-directed approach, our lead compound, GP1681, targets the underlying cause of life-threatening respiratory distress, cytokine release syndrome, by modulating the body’s natural immune response to sickness or disease. We are committed to developing first-in-class, best-in-class products that meet a major medical need now and into the future.

Miami, FL/June 22, 2020 - Quotient Sciences, a global pharmaceutical development, clinical and commercial manufacturing organization, announced today the completion of a $1 million pharmacy and laboratory expansion at its Miami, FL clinical pharmacology facility. 

The expanded pharmacy capabilities offer customers a quick and cost-effective way to start clinical testing, without the need for extensive CMC investment or API consumption at this early stage of development. Dose preparations can be made in “real-time”, enabling clients to make seamless adjustments to the dose or formulation and respond to changes in the first-in-human (FIH) protocol design.

The pharmacy’s compounding capabilities are differentiated in the marketplace as they are uniquely integrated with Quotient Sciences' broader formulation development and GMP clinical trial manufacturing capabilities at sites in the US and UK. This combined offering helps clients efficiently bridge from a fit-for-purpose Phase I formulation to a patient-friendly GMP drug product for subsequent Proof-of-Concept (POC) trials. All of this can deliver an accelerated timeline without the need for the customer to have to work with multiple vendors.

"Quotient Sciences is focused on providing our clients with solutions to get new medicines to patients faster." said Mark Egerton, CEO of Quotient Sciences. “When starting clinical development, our customers have a choice between pharmacy preparations or GMP drug product manufacturing. At Quotient, all options and program configurations are available for our clients, to help them reach their development milestones in the timeliest and most cost-effective way.”

The state-of-the-art pharmacy was built to ISO Class 5 and ISO Class 7 standards, following USP <795>, USP <797>, and USP <800> compounding guidelines to support both sterile and non-sterile drug programs. The facility is equipped with the necessary handling capabilities for highly potent and high-risk molecules, supporting a variety of oral and parenteral dosage forms. The pharmacy is located within Quotient Sciences clinical pharmacology facility, which features 144 clinical beds for performing first-in-human and other Phase I healthy volunteer trials.

For those with challenging molecules, clients can also leverage Quotient Sciences biopharmaceutics and formulation development expertise including a full range of solubility enhancement technologies including lipidic systems, micronization, spray drying, and hot melt extrusion, to produce solubilized intermediates and final dosage forms.

ANA Therapeutics, a Silicon Valley-based biotech startup, and Quotient Sciences, a leading provider of innovative drug development and manufacturing solutions, announced a partnership to support the manufacturing of ANA Therapeutics’ drug candidate, ANA001 (niclosamide capsules), which they are developing as a potential treatment for COVID-19. As part of the collaboration, Quotient Sciences will scale up the capsule formulation, characterize and optimize the manufacturing process and ensure continuity of drug product through clinical trials.

Laboratory experiments have shown niclosamide stops SARS-CoV-2, the virus that causes COVID-19, from replicating, making it a promising candidate for reducing the spread of COVID-19. Niclosamide was previously approved by the FDA as a treatment for tapeworm. Although not currently marketed in the U.S., it is on the World Health Organization’s List of Essential Medicines and has been used for decades to safely treat millions of people around the world.

“We have selected Quotient Sciences as our development and manufacturing partner and our plan is simple,” said Andrew Bartynski, COO, ANA Therapeutics. “Niclosamide has the potential to be an effective antiviral agent to combat COVID-19, and our top goal is to complete a clinical trial to determine its efficacy in treating patients with COVID-19. Quotient Sciences' speed and agility will play a key role in reaching that important milestone.”

Mark Egerton, Ph.D., CEO of Quotient Sciences, said, “We are proud to partner with ANA Therapeutics in their pursuit of a treatment to fight this coronavirus pandemic. Our experience and flexible manufacturing approaches will enable ANA Therapeutics to initiate clinical testing in an accelerated timeframe.”

Under the scope of the agreement, ANA Therapeutics will access Quotient Sciences' formulation and manufacturing expertise to develop and rapidly supply drug product for pivotal clinical trials in Q3 2020. The program will be conducted at Quotient Sciences' facility in Garnet Valley, Pennsylvania.

As of January 2021, ANA Therapeutics has been acquired by NeuroBo Pharmaceuticals, Inc. (Nasdaq: NRBO), a clinical-stage biotechnology company.

NOTTINGHAM, U.K.; Feb. 9, 2021 – Quotient Sciences, the drug development and manufacturing accelerator, announced that it has acquired Arcinova, the U.K.-based multiservice contract development and manufacturing organization (CDMO). With over 40 years of experience and 160 employees, Arcinova provides drug substance, drug product and bioanalysis services to over 200 pharma and biotech customers worldwide.

The acquisition expands Quotient’s service portfolio and will enable the integration of drug substance, drug product and clinical testing capabilities all under one organization — extending the 12-month drug development timeline savings already delivered by Quotient’s flagship platform Translational Pharmaceutics®. By cutting through silos and integrating a range of capabilities, outsourced development programs can be further simplified and accelerated, consistent with Quotient’s belief that molecules need to become cures, fast.

“I’d like to congratulate the Arcinova team on building an exciting business, and I am thrilled to be joining forces. Both businesses are similar in culture and aspire to help customers accelerate molecules from candidate selection through development and on to commercial launch,” said Mark Egerton, Ph.D., CEO of Quotient Sciences. “I’d also like to take this moment to thank our private equity partner, Permira, for supporting our ambitious growth plans.”

Professor Ian Shott, CBE, co-founder and executive chairman of Arcinova, said: “Since inception, we set out to build a unique organization that accelerates the development of new medicines for patients in need. We are delighted to move on to the next stage with Quotient as the perfect partner for Arcinova. Deep science, agility, flexibility and the drive for customer service excellence are the cornerstones of both businesses. I look forward to working with the Quotient team and Permira to deliver even greater value for our customers.”

As part of the deal, Arcinova’s minority equity partner, BGF, will exit the business, having backed its growth since 2018. Mark Bryant, BGF, said: “It has been a privilege to support the expansion of Arcinova’s world-leading CDMO facility at such a critical part of its growth journey. We wish the team all the best as it moves to the next stage with Quotient Sciences.”

RBC Capital Markets acted as exclusive financial advisor to Quotient Sciences. PwC provided financial and tax due diligence services and Latham & Watkins provided legal counsel. BGF received legal counsel from Weightmans. KPMG served as corporate finance adviser for Arcinova, and Womble Bond Dickinson provided legal counsel.

The CRO Leadership Awards recognizes the top performing outsourcing organizations in the drug development arena. For 2021, Quotient Sciences has been recognized with multiple 2021 CRO Leadership Awards, including two Champion Awards. 

For the 2021 CRO Leadership Awards, Clinical Leader and Life Science Leader teamed up with Industry Standard Research (ISR) to determine award recipients. 60 contract research organizations (CROs) were assessed on 20+ performance metrics in ISR’s annual CRO Quality Benchmarking survey. Survey participants were recruited from pharma and biopharma companies of all sizes and were screened for decision-making influence related to working with contract research organizations. Respondents only evaluate companies with which they have worked on an outsourced project within the past 18 months. This level of qualification ensures that survey responses are based on actual involvement with CROs and clear experiential data. 

The Company received leadership awards in five of the overall six categories. The categories included: Capabilities, Compatibility, Expertise, Reliability, Quality, and Phase IV, each further divided into three groups – Big Pharma, Small Pharma, and Overall. Additionally, champion awards are given to companies that score 11/2 standard deviation more above the weighted average in each of the categories and are deemed “top performers”.

Champion Award Winning Categories:

• Expertise (Overall)
• Quality (Overall)

Leadership Award Winning Categories:

• Capabilities (Overall, Small Pharma)
• Compatibility (Overall, Small Pharma)
• Expertise (Overall, Small Pharma)
• Reliability (Overall, Small Pharma)
• Quality (Overall, Small Pharma) 

Featured Interview with Mark Egerton, CEO of Quotient Sciences with Global Business Reports

Can you provide an introduction to Quotient Sciences?

With operating facilities in both the UK and US, we deliver uniquely integrated programs or a range of tailored services that allow our customers to accelerate their development timelines and get life-changing medicines to patients faster. Approximately 12 years ago, we created a new innovative platform called Translational Pharmaceutics™ which integrates disciplines around drug product manufacturing and clinical testing that are traditionally found in different silos in the outsourcing industry. By integrating these activities and very closely aligning workflows around manufacturing and clinical testing, we demonstrated that we are able to save at least 12 months on the drug development timeline. This translates into helping customers accelerate new medicine development, save time, money and give a better chance of a good outcome from the development program. If you take those 12 months and translate that into economic value to a customer, it comes out at around US$200 million for every molecule that makes it to market. The financial benefits were quantified in a 2020 publication written by the Tufts Center for the Study of Drug Development.

What are some of the ways in which Quotient helps clients conserve cash?

The integrated approach that Quotient has developed allows for a rapid “make-test” cycle that is under a single flexible clinical protocol. This enables you to manufacture a formulation and dose it in a clinical study to see the impact of that formulation and how it works to deliver the active substance. Then you can modify the formulation composition to improve the delivery by using real-time clinical data. This can be done in 14-day test cycles. Therefore, as the clinical program is developing, we can iteratively use clinical data to deliver an optimal drug product composition. We can then seamlessly take that product all the way through to proof-of-concept and on to commercial manufacture if the molecule is successful.

What was the Impetus for Quotient’s acquisition of Arcinova?

What interested us in Arcinova is their expertise in early-stage drug substance and bioanalysis work, accompanied by their isotope labelling capabilities that are complementary to our existing 14C ADME services. With regard to drug substance, we see a great opportunity in integrating drug substance services into our platform. There are many occasions where we cannot start our program on the planned timeline because the customer is not able to deliver their drug substance to us. Therefore, we feel it is a great opportunity to integrate drug substance, drug product and clinical testing capabilities. Both Arcinova and Quotient both are able to work on the molecules early, just as they are coming out of discovery.

What is Quotients approach to hiring and retaining top talent?

Human talent is the fundamental ingredient for any service organization like ours. As the industry pipeline has expanded, the funding has expanded, the number of molecules expanded, and, as a result, there is more work to do. Talent management and talent acquisition have become crucial aspects of business development. From my perspective, there are some simple ground rules for how we develop the business. First, we must be an exciting place to work, because talented people want to work in places where they feel they can make a difference, not just in how they do their job, but in what the company is trying to contribute into the general initiative around healthcare and wellbeing. We have always strived to have this differentiated position and that has served us well in terms of attracting talent. Secondly, career growth and personal development is essential. When talent comes to Quotient, you must give people the space to develop and spread their wings and achieve their potential, because if they achieve their potential, then that is only going to benefit the business. Employees put their trust in companies to help their careers, and if companies cannot support them to develop, then employees will go somewhere else.

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Addressing Challenges in Oncology Drug Development

The World Health Organization (WHO) estimates that cancer accounted for nearly 10 million deaths in 2020 with the most common cancers occurring in the breast, lung, colon/rectum, and prostate. The growing demand for new and improved treatments is clear, as is the need to streamline oncology drug development so new treatments can reach those in need, faster. 

Learn how pharma and biotech companies can leverage integrated services from a small molecule CRDMO partner to expedite the clinical trial process for oncology small molecule therapeutics. 

The role of accelerated approval pathways and how Translational Pharmaceutics® further accelerates oncology therapies

The limited effectiveness of existing oncology drugs requires novel approaches to accelerate the clinical trial process. Accelerated approval pathways, which allow the NDA application process to commence from Phase II onwards, require the early submission of a high-quality chemistry, manufacturing, and controls (CMC) package. This push to expedite timelines only increases the risk of commercializing a drug product production process that is not fully optimized or scalable.

For almost two decades, the Quotient Sciences Translational Pharmaceutics® platform has been able to remove extra time and steps from the oncology drug development process. Translational Pharmaceutics® consolidates drug product and clinical testing within a single organization and program to help reduce the burden of outsourcing, ensuring a phased, resource-efficient approach to clinical trials. We can help ensure the scalability of an optimal drug product, with the ability to modify dosage forms for additional areas of need, such as pediatric patients. This further reduces the time required for the clinical phase and minimizes the amount of drug substance needed. 

A recent achievement for a customer's oncology program involved a rapid method for conducting first-in-human studies with a single ascending dose (SAD) study. Within this study, multiple formulations were developed within a single design space, and a leading formulation was identified and validated for patient trials in just 12 months.

Overcoming challenges in emerging oncology modalities

Emerging modalities of oncology treatments, such as immunotherapy, and new chemical entities (NCEs) present increasing challenges in physical form, morphology, and chemical complexity. Therefore, selecting a drug development partner with proven experience in delivering these types of programs is crucial. 

Our approach involves an early understanding of the biopharmaceutics (DCS classification) during the drug development process, combined with expertise in process chemistry, analytical technology, and formulation development. We mitigate risks in subsequent development phases by gaining early insight into the compound's druggability, guaranteeing a high-quality CMC package that aligns with the accelerated approval process for oncology trials.  

Quotient Sciences first brought meaningful innovation to the pharmaceutical industry in 2008 with Translational Pharmaceutics®. Contact us today to discuss how it can be applied to your next drug program.