Susan Haigney

AAPS PharmSci360 Challenges in Peptide-Based Drugs

The development of oral peptide-based drugs presents unique challenges, specifies Brittany Hayes, PhD, Highly Potent & Oncology Platform Director at CordenPharma, due to the harsh environment of the gastrointestinal tract, highly acidic stomach, and enzymes that degrade peptides. “New manufacturing technologies and formulation techniques have shown to increase bioavailability by a few percentage points,” says Hayes. “But there's a lot of variability here, including variability from one patient to the next and also in the same patient from one day to the next day. One of the big ones that's been out there is permeation enhancers.”

Analytics is an important factor for the development of peptide-based drugs, highlights Hayes, because degradation products may be difficult to detect and quantify. “And then, with the use of these permeation enhancers, there needs to be simultaneous dissolution of the permeation enhancer and the peptide,” she says. “So, there may be some challenges here with analytical methods.” She also points out these novel excipients may require more regulatory qualifications and could be treated differently than conventional excipients.

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Pharmaceutical Technology® caught up with Brittany Hayes, PhD, Highly Potent & Oncology Platform Director at CordenPharma, after AAPS PharmSci 360 to talk about the challenges and quality requirements involved in the development and manufacture of peptide-based oral dosage forms. 

AAPS PharmSci 360: Challenges in Peptide-Based Drugs

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The University of Texas MD Anderson Cancer Center announced on Nov. 8, 2024 that it is creating the Institute for Cell Therapy Discovery & Innovation for the development of cell therapies for cancer, autoimmune diseases, and infections. The institute will bring scientists and clinicians together to provide insight on immunology and cell engineering with $80 million support from philanthropic organizations and institutions.

Led by Katy Rezvani, vice president and head of the Institute for Cell Therapy Discovery & Innovation, the new institute will integrate MD Anderson’s different research areas with the goal of accelerating discovery and development of new cell therapies from preclinical through clinical phases. This effort includes the James P. Allison Institute and Institute for Data Science in Oncology. External researchers and bio/pharmaceutical companies will also be part of the collaborative effort.

“Cell therapies have delivered profound results for patients with hematologic cancers, but there remain too many patients that do not benefit. It is critical to our mission to bring these promising therapies forward as options for patients with cancer and other conditions,” Rezvani said in a press release (1). “Through our discoveries, we aim to provide many more patients with effective cell therapies that are available as off-the-shelf treatment options, limiting the need for lengthy hospital stays and associated costs.”

“MD Anderson clinicians and researchers have been instrumental in shaping the cell therapy field, and we are proud to take this important step into the future,” said Peter WT Pisters, president of MD Anderson, in the release. “The Institute for Cell Therapy Discovery & Innovation is a key piece of our institutional strategy, as we focus on cancer breakthroughs to improve patient outcomes. Our world-class facilities, exceptional talent and unique research environment will enable our teams to deliver transformational new medicines and to further our efforts to maximize our impact on humanity to finally end cancer.”

Cell therapies use a patient’s immune cells as building blocks to create treatments. MD Anderson has performed clinical trials on FDA-approved chimeric antigen receptor (CAR) T cell therapy products targeting CD19 and BCMA for B-cell lymphomas, leukemias, and multiple myeloma. The institute also advanced CAR natural killer (NK) cells into clinical studies patients with lymphoid malignancies, based on cord blood-derived CD19 CAR NK cell therapies developed by Rezvani and her team. Additional research by the group has been done for cell therapies in solid tumors, including adoptive T-cell receptor therapy targeting MAGE-A4 for patients with multiple solid tumor types.

“For years, our talented scientists and clinicians have been at the forefront of discovery, understanding and development of novel cell therapies,” said Giulio Draetta, chief scientific officer at MD Anderson, in the release. “By integrating with experts across the research and clinical enterprise, the Institute for Cell Therapy Discovery & Innovation will be able to create important new treatments, tailored to unmet patient needs, in ways only possible here.”

MD Anderson. MD Anderson Launches Institute for Cell Therapy Discovery & Innovation to Deliver Transformational New Therapies. Press Release Nov. 8, 2024.

Articles

The new Institute for Cell Therapy Discovery and Innovation will utilize expertise to develop cell therapies for cancer, autoimmune diseases, and infections.

MD Anderson Launches Cell Therapy Institute

Members of academia and industry in the United Kingdom are highlighting the need for training within the pharma manufacturing field after Chancellor of the Exchequer, Rachel Reeves, announced in the Autumn Budget that there will be £520 million (US$675 million) made available to develop drug manufacturing capabilities in the UK (1). The budgetary funding allocation will begin with an increase in manufacturing capacity so that the UK can better respond to healthcare emergencies. But some are saying that the funds would be better suited in training of personnel.

“This announcement in the Budget to support life sciences is a welcome step for the UK medicines manufacturing sector,” said Professor Ivan Wall, co-director of Resilience, the UK’s first Medicines Manufacturing Skills Centre of Excellence, in a press release (2). “However, there is an acute skills shortage that must be addressed to ensure we have trained staff ready to work in the sector.”

Resilience, which was created to address the shortage of skills in the pharmaceutical industry within the UK, is a two-year project funded by the Office for Life Sciences in the UK Government’s Department for Science, Innovation & Technology that is managed through Innovate UK. The center’s interest, as would be expected, is to ensure that talent is being focused on. Resilience will be providing industry training courses that address issues such as digital technology, artificial intelligence, data analysis, and environmental sustainability. The center will be partnering with universities across the UK to develop the program, which will include in-person and remote training courses for advanced laboratory and manufacturing skills at the academic level.

“A major consideration for success in building this capability will be in ensuring a strong supply of talent to maximize productivity across new facilities,” said Wall in the release. “Talent is in short supply across the UK Life Sciences sector and that is where projects like Resilience can help, by building the ecosystem to maintain a strong, internationally competitive sector and ensure patients have access to the best drugs through the NHS [National Health Service].”

Sustainability is also a goal of the center. “There is a great opportunity to design with environmental sustainability principles embedded,” Wall said. “Around 25% of NHS emissions are in the supply chain, so our approach using VR [virtual reality] training will reduce plastics and other waste, helping the industry deliver net zero medicines manufacturing.”

Autumn Budget 2024: Fixing the Foundations to Deliver Change

2. Resilience. UK’s Medicines Manufacturing Skills Centre Welcomes Budget’s £520 million for Manufacturing but Says the Priority Must be Skills Development. Press Release. Nov. 6, 2024.

A £520 million investment for manufacturing capacity was announced by Chancellor of the Exchequer, Rachel Reeves, but academic and industry leaders stress the money should be used to train personnel.

UK Medicines Manufacturing Skills Centre Stresses Skill Development after Budget Announcement

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Bespak, a contract development and manufacturing organization that specializes in inhalation products, announced on Nov. 6, 2024 that it is partnering with Orbia Advance Corporation, S.A.B. de C.V (BMV: ORBIA) Four & Energy Materials (Orbia Fluor & Energy Materials) to transition to climate-friendly inhalers. As part of the collaboration, Orbia, a supplier of fluoroproducts and technologies, will provide Bespak with its low global warming potential (GWP) propellant, Zephex 152a for use in Bespak’s pressurized metered dose inhalers (pMDIs).

Bespak is making the transition to the GWP propellant as part of the overall pMDI industry’s commitment to sustainable solutions. The company verified the use of producing pMDI formulations with GWP propellants with the assistance of its network of partners and its good laboratory practice (GLP) lab-scale testing, as well as its clinical- and commercial-scale good manufacturing practice (GMP) capabilities. Bespak will also utilize Orbia’s clinical-scale GLP and GMP capabilities.

The two companies will work closely at their locations in North West, England, with support from Bespak’s King’s Lynn, United Kingdom, location, which has conducted research on a range of valves and actuators.

“We are committed to leading the transition to low GWP propellants in pMDIs, and in collaboration with Orbia Fluor & Energy Materials, we will enable customers to progress their inhaler portfolios utilizing Zephex 152a,” said Chris Hirst, CEO of Bespak, in a press release (1). “Our goal is to convert as many formulations as possible to maintain patient access to pMDIs as global regulation evolves, and we look forward to working with Orbia Fluor & Energy Materials to provide customers with a pathway to commercialization at our Holmes Chapel site.”

“This is another step forward in bringing pMDIs using our low GWP medical propellant Zephex 152a to the market,” said Markus Laubscher, general manager of Orbia Fluor & Energy Materials Pharma Business Unit, in the release. “We are excited to extend our industry collaborations to Bespak who bring the needed capabilities to the table, from their expertise in valves and actuators, to their demonstrated commitment to clinical and commercial-scale product manufacturing.”

Bespak has made recent investments in its development services through its market approval services for all pMDI formulations and propellants. It has also increased capacity for commercial supply. In October 2024, the company announced that, in connection with H&T Presspart, it had added a GMP pilot-scale filling line for pMDIs to produce GWP propellants HFDA-152a and HFO-1234ze (2). The new filling line provide access to small-scale GMP capabilities for development programs and clinical trials.

“This new low GWP pilot-scale filling capability addresses the short-term market need for clinical trial supply and will help pharma companies to advance their low GWP development programs towards commercialization,” Hirst said in the press release. “When added to our rapidly expanding low GWP commercial-scale capability, it is clear that we can now offer customers a complete transition pathway.”

“H&T Presspart is committed to supporting the industry in transitioning to low GWP propellants,” said Christian Krätzig, president of H&T Presspart, in the release. “In our partnership with Bespak, we are now leveraging our combined expertise to create the infrastructure needed for small-scale manufacturing with low GWP propellants. The launch of a GMP pilot-scale filling line is an important step forward, and we are excited about future collaborations that will help to create a more sustainable pMDI platform for the next generation.”

Bespak. Bespak and Orbia Fluor & Energy Materials Unite to Accelerate Transition to Climate-friendly Inhalers. Press Release. Nov. 5, 2024.

Bespak. Bespak & H&T Presspart Announce Availability of GMP Pilot Line for Low GWP pMDIs. Press Release. Oct. 8, 2024.

The companies will work to create climate-friendly pMDIs using Orbia’s low global warming potential propellant.

Bespak and Orbia Fluor & Energy Materials Collaborate on Climate-Friendly Inhalers

Aptamer Group announced on Nov. 7, 2024 that one of its customers has advanced use of the company’s Optimer binders for the commercial phase of its product. The customer has used the Optimer delivery vehicle for the product’s development phase and Aptamer shipped test materials to the customer in October 2024.

According to Aptamer, the customer has validated the performance of the delivery vehicles, indicating the vehicles can target the required cell type. The vehicles have the potential to be used as part of a precision therapy. This would create downstream licensing revenue for Aptamer.

The customer also found that Optimer showed binding to the target cells from a panel of animal species, which makes the delivery vehicle desirable for preclinical development. “Due to the targeting specificity, multiple species binding, and reproducibility of the results, the customer has committed to progressing to the final commercial development stage for the therapeutic delivery vehicle,” Aptamer stated in a press release (1).

According to Aptamer, targeting genetic medicines to specific cell types is a challenge. Highly selective delivery vehicles address this challenge by targeting these cell types, which has been difficult in the past. The company is developing delivery vehicles that target fibrotic liver cells, creating progress for genetic medicine payloads.

“We are delighted with our customer’s decision to advance to the final stage of Optimer development. The customer’s results align with those seen within our own laboratories and validate the hard work of our scientific team to develop novel, high-performance delivery vehicles,” said Arron Tolley, chief executive officer of Aptamer Group, in the press release. “As this Optimer advances through the final development stages, we continue to move closer to demonstrating the strength of our Optimer platform in generating high-value, therapeutic targeting assets. This represents our second drug delivery asset with licensing potential, alongside our liver fibrosis targeting Optimer, which has already shown good effectiveness in delivering functional genetic medicines to specific cells. These could enable new approaches to precise drug delivery across the field of genetic medicines whilst underpinning our business model with passive income from licensing. We look forward to updating shareholders on future progress in due course.”

Earlier in 2024, the company announced an agreement with AstraZeneca to evaluate the use of Optimer for targeted delivery of small interfering RNA (siRNA). Aptamer will conduct in-house experiments to assess the effectiveness of the delivery vehicle with AstraZeneca’s siRNA as part of the agreement.

“Delivery of siRNA to precise cell types and tissues with successful cell internalization remains a significant challenge for the wider therapeutic application of the technology. Despite this limitation, the siRNA market was still valued at over $13 billion in 2023. Optimer technology could represent a paradigm shift in the targeted delivery of siRNA molecules, due to the high levels of selectivity, high affinity, and simple conjugation of siRNA payloads, offered using Optimer delivery systems as non-viral vectors. If successful, Optimer-enabled delivery of siRNA could lead to the development of novel compounds that have significant advantages over current cell and tissue-targeting methods,” the company stated in a press release (2).

“We are really excited to work with AstraZeneca to evaluate and optimize our Optimer delivery vehicles,” said Tolley in the release. “Partnerships such as this will enable Aptamer Group to make rapid progress in this area, which is a key focus for Optimer technology. Targeted delivery to specific cell types remains a critical unmet need in many applications within the tissue targeting space and, as such, has been part of our strategic focus to support the development of binders with the potential for long-term, high value. Our initial dataset in Optimer targeted delivery has raised significant interest from multiple parties. We are eager to advance to animal model testing and delighted to continue collaborating with AstraZeneca in this endeavor. Reaching proof of principle in animal models will derisk the Optimer delivery platform and bring us closer to delivering targeted and effective gene therapies for patients.”

Aptamer Group. Aptamer Extends Agreement with Genetic Medicines Customer. Press Release. Nov. 7, 2024.

Aptamer Group. Agreement to Explore Optimer Vehicles for Targeted Delivery of siRNA. Press Release. July 3, 2024.

A genetic medicines customer has selected the company’s binders for commercial development of the customer’s product.

Aptamer Extends Agreement for Drug Delivery Vehicles

Avid Bioservices, a biologics contract development and manufacturing organization (CDMO), announced on Nov. 6, 2024 that it has entered into a merger agreement, valued at approximately $1.1 billion, with GHO Capital Partners and Ampersand Capital Partners.

Under the terms of the agreement, GHO and Ampersand will acquire all outstanding shares held by Avid’s stakeholders for $12.50 a share in cash, which is a 13.8% premium to the Nov. 6, 2024 closing price of $10.98 and a 21.9% premium to Avid’s 20-day volume-weighted average share price. The transaction is expected to close in the first quarter of 2025, subject to customary closing conditions, approval by Avid’s stockholders, and receipt of required regulatory approvals.

“Since our founding, Avid Bioservices’ business has grown by evolving to meet our customers' broad range of development and manufacturing needs. After years of investment and expansion, now is the right time to move forward as a private company with new owners that will support our next phase,” stated Nick Green, president and CEO of Avid Bioservices, in a press release (1). “In evaluating this transaction, our [b]oard considered a range of alternatives and determined that it provides our stockholders significant, immediate, and certain cash value for their shares. Partnering with GHO Capital and Ampersand Capital Partners allows us to build on our strong foundation by accessing their significant knowledge base, network and capital to position the business for the future with our customers.”

“We are excited to announce this recommended cash acquisition of Avid,” said Alan MacKay and Mike Mortimer, managing partners of GHO, in the release. “As experienced CDMO industry investors, GHO brings deep expertise and experience to support Avid's management team going forward. Our mission at GHO is to make healthcare better, faster, and more accessible and at the heart of this is enabling efficient, high-quality manufacturing of innovative treatments. Avid exemplifies this perfectly—the [c]ompany operates in high-growth markets, producing complex biologics for leading pharmaceutical and biotech innovators at both the clinical and commercial stages. Avid’s recent investments, both in capacity and its exemplary team, position it strongly for future growth. We look forward to working with the Avid team to unlock the [c]ompany’s full potential through our established playbook of expanded offerings, talent investment, and greater geographic reach.”

“Avid has long been a trusted provider of biopharmaceutical development and manufacturing services, and we have tremendous respect for its team’s expertise, its broad spectrum of customized services, and its strong regulatory track record. We look forward to leveraging our deep industry experience, focused strategy, and collaborative approach to drive growth,” said,David Anderson, general partner ofAmpersand, in the release.

Avid offers a range of biopharmaceutical process development, current good manufacturing practice (CGMP) clinical, and commercial manufacturing services, which include CGMP clinical and commercial drug substance manufacturing, bulk packaging, release and stability testing, and regulatory submissions support. It also provides process development activities for early stage programs, such as cell line development, upstream and downstream development and optimization, analytical methods development, testing, and characterization.

1. Avid Bioservices. Avid Bioservices to be Acquired by GHO Capital Partners and Ampersand Capital Partners in $1.1 Billion Transaction. Press Release. Nov. 6, 2024.

The merger agreement is valued at approximately $1.1 billion.