Behind the Headlines Episode 27

Ask the Expert

Small Molecules, APIs, and Excipients—Trends, Challenges, and Opportunities

Drug Digest September 2025

Artificial intelligence, machine learning, and novel instruments are helping drug developers.

Enhancing Bioanalysis and Drug Development with Advanced Tools and Technologies

J.P. Morgan Report Lists Biologics, Obesity, China

Top Trends Reshaping Pharma R&D

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

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Almost three years to the day since announcing the establishment of its joint artificial intelligence (AI) laboratory, the biotechnology company PostEra said it is increasing its partnership with Pfizer to a total value of $610 million, primarily through the launch of a new antibody-drug conjugate (ADC) collaboration (1).

In a press release dated Jan. 7, 2025, PostEra said it will receive $12 million up front and may be eligible for additional, milestone payments, and also tiered royalties on any approved products that result from the collaboration (1).

The two parties plan to leverage PostEra’s AI platform, called Proton, in the advancement of a number of programs including small-molecule therapeutics as well as ADCs, for the latter of which Proton will be used to optimize payload properties, according to the release.

"We're pleased to significantly expand the use of PostEra's Proton platform,” Alpha Lee, PostEra chief scientific officer, said in the release. “This builds on peer-reviewed publications with Pfizer validating the real-world impact of AI-driven drug discovery in hitting preclinical milestones faster than anticipated."

The alliance between PostEra and Pfizer over the past three years has already advanced several small-molecule programs, and the AI Lab itself was built on a pre-existing Generative Chemistry partnership that dates back to the two companies first entering into strategic collaboration in December 2020 (2–4).

"This third partnership with our long-term collaborators at Pfizer underscores Proton's depth and strength in making a meaningful impact on real-world drug discovery campaigns," Aaron Morris, PostEra, said in the January 7 release.

PostEra’s last update on the AI Lab came in March 2024, when it said that one of the lab’s programs had achieved its first scientific stage gate 40% faster than predicted, a second program was making similar progress, and a third target was being nominated by Pfizer (2).

When first announced on Jan. 11, 2022, the value of the AI Lab was originally estimated by PostEra and Pfizer to be approximately $260 million (3).

“Working together, our teams have been able to rapidly apply PostEra’s novel AI technology to drug discovery efforts, which may in turn help accelerate the identification of potential medical breakthroughs for patients in need,” said Patrick Verhoest, head of medicine design at Pfizer, said in 2024 (2).

The initial focuses of the drug discovery programs prioritized by PostEra and Pfizer were oncology and COVID-19 antiviral therapeutics; in fact, as of 2022, PostEra was responsible for the largest open-science drug discovery effort in the world, “COVID Moonshot” (3).

As part of that December 2020 agreement, PostEra also retains ownership rights to all algorithms developed during its collaboration with Pfizer (4).

1. PostEra. PostEra Announces Expansion to $610M in Their AI Drug Discovery Collaboration with Pfizer. Press Release. Jan. 8, 2025.
2. PostEra. PostEra Provides Update on Progress of the Pfizer-Partnered AI Lab. Press Release. March 27, 2024.
3. PostEra. PostEra Announces $260M Multi-Target Strategic AI Lab Collaboration with Pfizer. Press Release. Jan. 11, 2022.
4. PostEra. PostEra Enters a Multi-Year Strategic Partnership with Pfizer Inc. to Advance Machine Learning for Drug Discovery. Press Release. Dec. 7, 2020.

Articles

The AI Lab was launched almost exactly three years ago and has produced several programs so far, at least one of which achieved its first scientific stage gate 40% faster than the teams originally forecasted.

PostEra Expands Pfizer Partnership with AI Lab and ADC Collaborations

Feliza Mirasol is the science editor for 

Argobio announced on Jan. 7, 2025 that it has launched Inverna Therapeutics, a new, Denmark-based biotech company specializing in innovative RNA therapeutics, with the University of Southern Denmark as co-founder. The new company will focus on severe genetic diseases, starting with Huntington’s disease, for which the company has a lead program.

Inverna’s technology platform comes from research conducted by Professor Brage S. Storstein Andresen, an expert in RNA splicing and antisense technology who holds the position of co-founder and chief scientific officer at Inverna (1). Inverna’s goal is to overcome the limitations of conventional RNA therapeutics, and it will do so by harnessing the potential of sequence-based splice modulation, which will allow the company to create safer and more effective treatments for a wide range of debilitating diseases, according to a press release.

“We are thrilled to introduce Inverna to the world,” said Poul Sørensen, CEO of Inverna and partner and entrepreneur-in-residence at Argobio, in the release (1). “Our team, combined with the strong support of Argobio and the University of Southern Denmark, is uniquely positioned to develop transformative therapies that address significant unmet medical needs. Leveraging our proprietary insights into RNA splicing modulation, our pseudo-exon targeting technology offers a potential solution to limitations of current RNA therapeutics by enabling precise, sequence-based and allele-specific targeting with minimal off-target effects.”

Argobio is a European biotech start-up studio, based in Paris, that has played an important role in establishing Inverna. The studio sources early-stage therapeutic projects from leading European academic research institutions and focuses on rare diseases, neurological disorders, oncology, and immunology. Argobio selects and incubates these projects with the goal of developing them into fully-fledged biotech companies and advancing them to significant Series A financing. The studio offers extensive expertise in novel drug discovery and development with the help of a team of highly experienced biotech entrepreneurs. With an initial investment, strategic guidance, and operational expertise, Argobio empowered Inverna to accelerate the development of its innovative RNA pipeline.

“It is fantastic to have the opportunity to translate our many years of research on pre-mRNA [messenger RNA] splicing regulation in human disease into new RNA precision medicines,” said Andresen in the release. “We are excited and eager to unleash the potential of our new discovery engine to develop new RNA therapeutics for untreatable diseases.”

Argobio builds companies to address critical medical needs. The companies that it establishes are based on breakthrough scientific discoveries and innovative approaches, according to Thierry Laugel, chairman at Argobio and managing partner at Kurma Partners.

“We are very pleased to transform another outstanding academic project into a promising industry player. Inverna fits perfectly into our model, with access to cutting-edge science and our unique expertise in building and running biotech companies,” Laugel said in the release.

The University of Southern Denmark was also instrumental in laying the scientific groundwork for Inverna’s innovative approach.

“The launch of Inverna Therapeutics exemplifies the University of Southern Denmark’s commitment to transforming world-class research into real-world impact," said Thomas Schmidt, head of Technology Transfer at the university, in the press release. “Through our collaboration with Argobio and the visionary leadership of Professor Brage Storstein Andresen, we are proud to contribute to the development of groundbreaking therapies that address critical unmet medical needs.”

Next-generation RNA Company Inverna Therapeutics Launched by Argobio and University of Southern Denmark

Using splicing technology, the new company aims to innovate safer and more effective RNA therapies for severe genetic diseases.

Argobio and University of Southern Denmark Launch New Next-Gen RNA Company, Inverna Therapeutics

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FDA announced the publication of a pair of guidance documents, one as a draft and one in its final form, on Jan. 7, 2025 (1,2). The deadline for comments on the draft guidance to be considered for its final version has been set for April 8, 2025 (2).

That guidance, “Developing Drugs for Optical Imaging,” concerns those drugs which are used in conjunction with imaging devices, intended as intraoperative aids either for detection of pathology (i.e., tumors), or to enhance conspicuity for otherwise normal anatomical structures (2).

As its name suggests, optical imaging uses light in conjunction with imaging drugs and devices, and FDA considers its guidance necessary because of a “burgeoning interest” in development of novel drugs and devices to further assist in a variety of standard surgical procedures (2).

Meanwhile, the final guidance, “Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products: Questions and Answers,” bears the same title as a revised draft guidance from October 2023, which in turn replaced a draft guidance issued as far back as March 2014 entitled “Distributing Scientific and Medical Publications on Unapproved New Uses--Recommended Practices”—itself replacing a previous final guidance, “Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices,” issued in January 2009 (1).

Through its many incarnations, FDA summarized the present form of this document by saying it intends to describe the agency’s enforcement policy when it comes to communications of scientific information initiated by firms, detailing unapproved uses of those firms’ medical products to healthcare providers (HCPs) who are tasked with prescribing or administering the products to patients, whether or not the products are cleared or approved. However, FDA said pending a decision by its Office of Management and Budget on collection of certain information, the final guidance is not meant for current implementation.

“A firm’s communication about unapproved uses of its approved/cleared medical product could be evidence of the firm’s intended use for such product, and, depending on the facts and circumstances, may be relevant to establishing that the firm has distributed a medical product that fails to comply with applicable premarket requirements or is otherwise misbranded or adulterated,” the guidance says (1). “At the same time, in certain circumstances, HCPs may be interested in scientific information about unapproved uses of approved/cleared medical products to inform clinical practice decisions for the care and management of their individual patients.”

FDA reminded the public, in both cases, that online or written comments can be submitted on any guidance at any time, even if the guidance is considered “final” (1,2).

Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical ProductsQuestions and Answers

, Revision 2 (CDER/CBER/CDRH/CVM/OC, January 2025).
2. FDA, 

The final guidance is a revision of a policy that has existed in some form since at least 2009, while a separate, draft guidance will accept public comment for consideration for its final version through April 8.

FDA Publishes Two Guidance Documents, One in Final Version

In a press release on Jan. 7, 2025, Phillips Medisize’s parent company, Molex, announced the completion of Phillips Medisize’s acquisition of Vectura Group from Vectura Fertin Pharma, of Chippenham, United Kingdom, a subsidiary of Philip Morris International (1). Phillips Medisize, a global contract development and manufacturing organization which designs and makes products for the pharmaceutical drug delivery, 

 diagnostic, and medtech markets, now adds Vectura’s inhalation capabilities to its stable of services.

The announcement closes a transaction which had previously been disclosed by the two sides involved in September 2024 (2). At that time, the parties expected the deal to close by the end of 2024, meaning official confirmation comes just a week past that deadline.

“The Vectura team is delighted with the completion of the acquisition,” said Geraldine Venthoye, PhD, the chief scientific officer of Vectura Fertin Pharma who has now been appointed to the same post, as well as vice president, for the Phillips Medisize Medical business (1). “We are excited about the opportunities and scale of Phillips Medisize, which will allow us to deliver our formulation and combination product expertise to more pharmaceutical customers as part of end-to-end pharmaceutical development.”

“The acquisition of Vectura reflects our commitment to advancing industry-leading medical capabilities for our customers,” said Molex CEO Joe Nelligan in the January 7 press release (1). “Together Phillips Medisize and Vectura will unlock significant growth potential to support the growing need for inhalation therapies.”

Phillips Medisize itself had previously been acquired by Molex, whose headquarters are in Lisle, Ill., in 2016 (1). The company said in the press release that adding Vectura’s services would enhance its capacity for pharmaceutical R&D.

Vectura’s proprietary technology, plus its experience in the field of combination product development, come to Phillips Medisize in the transaction; this includes dry powder inhalers, metered dose inhalers, nasal inhalers, and nebulizers, according to the press release (1). Among Vectura’s other offerings are pharmaceutical analysis, process development, technical transfer, clinical trial supplies, and regulatory services.

“Phillips Medisize will continue to expand the services we offer pharmaceutical companies thanks to the acquisition of Vectura, particularly in inhalation, to help meet growing patient needs,” said Paul Chaffin, president of Phillips Medisize. “Together Phillips Medisize and Vectura are uniquely positioned to collaborate with leading pharmaceutical customers to develop innovative products that address the growing global demand for new therapies to treat chronic respiratory diseases like asthma and COPD [chronic obstructive pulmonary disease], as well as non-respiratory conditions.”

With a workforce of already more than 6000 covering 30 job sites in North America, Europe, and Asia, Phillips Medisize will add approximately 350 employees with the acquisition of Vectura (1). Among those are some 1200 engineers and scientists.

1. Phillips Medisize. Phillips Medisize Expands Its Inhalation Drug Delivery Capabilities. Press Release. Jan. 7, 2025.
2. Phillips Medisize. Molex, A Parent to Phillips Medisize, Announces Agreement to Acquire the Vectura Group Limited, Expanding Its Drug Delivery Capabilities in Inhalation. Press Release. Sept. 17, 2024.

The transaction, which was first announced in September 2024, expands Phillips Medisize’s inhalation drug delivery capabilities.

Molex, Phillips Medisize Close Acquisition of Vectura Group

Denmark-based biotech startup Orbis Medicines recently won major funding to support its pursuit of developing oral alternatives to current biologic drugs, which are primarily administered parenterally.

The company announced on Jan. 6, 2025 that it closed a Series A funding round of $94 million (€90 million), which will go toward development of Orbis’ pipeline of next-generation oral macrocycle drugs, which the company has termed “

Cycles”. This latest funding round brings the total amount raised by the company to $121 million (€116 million).

Macrocycles bind to targets with higher affinity and selectivity than small-molecule drugs, but they have been historically challenging to develop as oral drugs. Orbis Medicines’ technology platform, 

Gen, systematically delivers macrocycle candidates—

Cycles—that are optimized for oral bioavailability. It has been this lack of oral bioavailability that has hindered therapeutic development of this class of molecules in the past (1). The 

Gen platform comprises multiple proprietary integrated elements in a “lab in a loop” system. It starts with hit-finding libraries containing 100 billion compounds. Using automated chemistry, the platform can synthesize and analyze up to 100,000 distinct synthetic macrocycles in weeks, which allows the company to discover candidates with the right properties to enable oral dosing and intracellular targeting.

The company’s pipeline is initially focused on 

Cycle candidates aimed against targets validated by blockbuster biologic drugs, which are delivered by injection, a route of administration that is not favorable with patients. The biopharma industry has been bending its efforts toward developing 

 for biologics that bypass the parenteral route, such as oral and inhaled biologic formulations (2). However, because biologics have more structural sensitivities than small-molecule drugs to factors such as pH and temperature, there are limits to their delivery, especially orally, such as degradation in the alimentary tract and an inability to overcome intestinal cell or mucosal barriers and first-pass metabolism (2). These limitations therefore open a path to alternative orally bioavailable drugs, such as 

“The Orbis Medicines team has impressed us with the data supporting 

Gen, which we believe is the world’s leading discovery engine for oral macrocycle drugs. We are thrilled to support not only their journey to the clinic, but also their longer-term vision as a leader in their field,” said Ed Mathers, partner, New Enterprise Associates (NEA), in the press release (1). NEA led the financing.

In addition to NEA as the lead financer, others that participated in the funding round include new investors Eli Lilly and Company, Cormorant, and the Export and Investment Fund of Denmark as well as founding investors Novo Holdings and Forbion. Morten Graugaard has been appointed as CEO of Orbis Medicines after having served nearly three years as executive chair of its board of directors.

“The company is advancing the potential of macrocycles by developing orally available 

Cycles—a format preferred by patients, physicians, and healthcare systems, particularly for chronic diseases,” said Graugaard in the release. “The interest we have received demonstrates the market appetite for 

Cycles as an oral approach to both validated biologic targets and targets undruggable by other modalities. We have a clear strategy for rapid value creation that leverages the unique capabilities of our 

Gen platform and are excited to advance this important new class of drugs for patients.”

Orbis Medicines Raises EUR 90 Million Series A Funding Round to Develop Pipeline of Oral Macrocycles

. Press Release. Jan. 6, 2025.
2. Mirasol, F. 

Exploring Innovative Means for Biologics Delivery

With the new $94 million (€90 million) funding, the company will develop its pipeline of oral macrocycle drugs, nCycles, against validated biologic targets.



With New Funding, Orbis Medicines to Develop Oral Macrocycles as Alternative to Biologic Drugs

Felicity Thomas is the former Associate Editorial Director of Pharmaceutical Technology, Pharmaceutical Technology Europe, BioPharm International.

Pharmaceutical Technology chats about continuous processes and regulatory considerations for processing equipment with Christian Dunne from ChargePoint Technology.

Using Continuous Processes and Automation to Remove Contamination Risk

Continuous production has been employed across many industries for some time to improve efficiencies, reproducibility, and quality. For the bio/pharma industry, continuous processes have come a long way, although semi-continuous is still more widely adopted.

“I think, of late, [continuous processing has] come a long way,” asserts Christian Dunne, director of Global Corporate Business Development at ChargePoint Technology. “We're still seeing there aren’t that many full continuous processes out there, but we do see a lot more semi-continuous processing. So that's where you're sort of combining two or maybe three processes together, and that that may be to start with, in terms of stacking them up, allowing the continuous process of material going from one process into another.”

Additionally, with the advent of more robotics, particularly in a cleanroom space, there is scope for companies to remove the operator from certain aspects of the process, which is helping to reduce risk, Dunne confirms. “Placing a robot into the process stream removes the operator, and that's the best thing you can do, from a containment perspective,” he says. “You have less risk for the operator, but you also have a vast improvement on the product quality as well. We do know from a microbiological perspective that generally it's the operator which is the most contaminating source on the process. So, if you can get [the operator] out of there, you've improved both the containment from the operator perspective, and also the product quality as well.”

Automation and reducing potential contamination are common threads throughout the European Union good manufacturing practice (GMP) Annex 1 guidance document, Dunne notes. “It's kind of a theme that's running through the whole of that document, isolating the operators from the process,” he says. “We're seeing lines now that are almost completely autonomous. And I think that [more automation is] going to be something that's going to come in the not-too-distant future.”

Christian Dunne, director of Global Corporate Business Development at ChargePoint Technology.

Christian Dunne is director of Global Corporate Business Development at ChargePoint Technology—a pharmaceutical containment and aseptic processing specialist company. Christian has worked in the bio/pharma industry for 20 years covering oral solid dosage manufacturing through to sterile processing and fill/finish manufacturing.

Videos

The Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Takeda's HYQVIA [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] to treat patients with agammaglobulinemia or hypogammaglobulinemia, Takeda announced on Dec. 27, 2024. Agammaglobulinemia and hypogammaglobulinemia are disorders characterized by very low or absent levels of antibodies. Patients suffering from these disorders have an increased risk of serious recurring infection caused by primary immunodeficiency (PID) or secondary immunodeficiency (SID) (1,2). This approval makes HYQVIA the first and only facilitated subcutaneous immunoglobulin (fSCIG) therapy to be made available as a treatment option for patients in Japan, according to a company press release. HYQVIA is also under review in Japan for additional indications.

The approval is based on data from two pivotal Phase III trials that evaluated the efficacy, safety, tolerability, and pharmacokinetics in Japanese patients with PID. Data from two Phase III clinical trials in patients with PID in North America were also included in the MHLW submission.

“We are delighted that HYQVIA, approved in more than 40 countries worldwide, has now been approved in Japan,” said Naoyoshi Hirota, regional head of Research & Development for Takeda’s Plasma-Derived Therapies Business Unit in Japan, in the press release (1). “The subcutaneous IG therapies currently available in Japan for patients with agammaglobulinemia or hypogammaglobulinemia require infusion once every week or every two weeks. We are proud to offer Japanese patients the first and only facilitated subcutaneous treatment option that offers a reduced dosing frequency of every three or four weeks.”

HYQVIA comprises a combination of one vial of IG 10% and one vial of recombinant human hyaluronidase PH20 (rHuPH20); rHuPH20 increases the dispersion and absorption of IG in the subcutaneous tissue. This increased dispersion and absorption allows for larger volumes to be infused at the infusion site, which in turn allows for less frequent dosing compared to other subcutaneous IG products. Meanwhile, this route of administration can avoid the need to access veins for delivering the therapy. Takeda noted in its press release that the ability to infuse a larger infusion volume is expected to increase administration flexibility for patients with agammaglobulinemia or hypogammaglobulinemia by decreasing the dosing frequency to once every three or four weeks, compared to the weekly or bi-weekly dosing schedule with conventional SCIG treatments.

“There is a high unmet need for plasma-derived therapies (PDTs) in patients in Japan, which is anticipated to increase as education and timely diagnosis rates continue to improve,” said Kristina Allikmets, head of R&D for Takeda’s Plasma-Derived Therapies Business Unit, in the release. “The approval of HYQVIA, the first and only facilitated SCIG treatment, is further evidence of Takeda’s commitment to add to the standard of care for patients in Japan. We look forward to continuing to bring new therapeutic options that support and enhance the experience of patients in our home country throughout the next decade.”

The approval follows Takeda’s previous announcement in March 2023 that the company is investing ¥‎100 billion (US$754 million at the time of the announcement; current conversion is US$635 million) into 

building a new manufacturing facility for plasma-derived therapies (PDTs) in Osaka, Japan

1. Takeda. Takeda Announces Approval of HYQVIA 10% S.C. (Subcutaneous) Injection Set in Japan for Patients with Agammaglobulinemia or Hypogammaglobulinemia. Press Release. Dec. 27, 2024.
2. Pimenta, F. M. C. A.; Palma, S. M. U.; Constantino-Silva, R.N.; Grumach, A.S. Hypogammaglobulinemia: A Diagnosis that Must Not Be Overlooked. 

 (10), e8926. DOI: 10.1590/1414-431X20198926
3. Takeda. Takeda to Invest 100 Billion JPY in a New Manufacturing Facility for Plasma-Derived Therapies in Japan. Press Release. March 23, 2023.

With this approval, HYQVIA [Immune Globulin Infusion 10% (human) with Recombinant Human Hyaluronidase] becomes the first and only facilitated subcutaneous immunoglobulin available in Japan to treat these disorders.

Takeda Receives Japanese Regulatory Approval for HYQVIA Subcutaneous Injection for Treating Agammaglobulinemia or Hypogammaglobulinemia

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FDA published a draft guidance document on Jan. 2, 2025 that provides considerations for complying with 21 

) 211.110 (1). This specific section of the CFR focuses on production and process controls for sampling and testing of in-process materials and drug products. The guidance, 

Considerations for Complying With 21 CFR 211.110, Guidance for Industry, Draft Guidance, 

applies to human drug products and biologics, but not to the manufacture of APIs. The guidance document also discusses how process models can be incorporated into commercial manufacturing control strategies.

Batch uniformity and drug product integrity current good manufacturing practice requirements state that manufacturing processes must be designed and controlled to ensure that in-process materials meet predetermined quality requirements. In the document, FDA states robust product and process development are crucial for establishing and maintaining control strategies throughout the product’s lifecycle so that quality attributes are obtained.

“To ensure conformance to drug product quality requirements, the manufacturer should identify which critical quality attributes and in-process material attributes to monitor and control,” FDA states in the document (1). “Section 211.110 allows flexibility in the in-process controls, and testing, or examinations that are employed to ensure that processes deliver in-process materials and drug products with the appropriate quality attributes. To ensure that drug products have the properties that they are represented to possess, the in-process materials used throughout the manufacturing process should be of consistent quality.”

In addition, the guidance details quality considerations for drugs manufactured using advanced manufacturing technologies (AMTs). “All manufacturers, regardless of whether they are using advanced manufacturing, should apply a scientific- and risk-based approach to controlling processes and ensuring drug product quality,” FDA states in the guidance document (1). “This approach should be based on robust product and process understanding. Manufacturers must maintain the process in a state of control over the life of the process to ensure drug product quality, even as materials, equipment, production environment, personnel, and manufacturing procedures change. Planning and executing a system that monitors process performance and drug product quality helps ensure that a state of control is maintained. An effective monitoring system helps maintain a state of control in multiple ways, which include helping manufacturers: ensure that processes and controls are continuously capable of producing a drug product of desired quality; and identify areas for continual improvement.”

Additional guidance on advanced manufacturing was also published by FDA in January, explaining requirements for those in industry that wish to participate in the agency’s Advanced Manufacturing Technologies Designation Program (2). The Advanced Manufacturing Technologies Designation Program was required under section 506L of the Federal Food, Drug, and Cosmetic Act to provide a framework for those requesting designation of a drug manufacturing method as an AMT. The program provides early interaction opportunities before application submission as a way to encourage adoption of AMTs (3).

Considerations for Complying With 21 CFR 211.110, Guidance for Industry, Draft Guidance

https://www.fda.gov/media/184825/download

Advanced Manufacturing Technologies Designation Program, Guidance for Industry

 (CDER, CBER, December 2024).
3. Haigney, S. FDA Publishes Final Guidance on Advanced Manufacturing Technologies. 

The draft guidance document provides recommendations for complying with 21 CFR 211.110.

FDA Releases Draft Guidance on Sampling and Testing of In-Process Materials and Drug Products

Innovent Biologics (Innovent), a China-based biopharmaceutical company specializing in treatments for oncology, cardiovascular and metabolic, autoimmune, ophthalmology, and other major diseases, announced on Jan. 2, 2025 that it has entered into a collaboration and exclusive license agreement with Roche. The companies will advance the development of IBI3009, Innovent’s novel delta-like ligand 3 (DLL3)-targeted antibody drug conjugate (ADC) candidate. The collaboration is aimed at bringing innovative treatment options to patients with advanced small cell lung cancer (SCLC).

Under the agreement, Roche receives exclusive global rights to develop, manufacture, and commercialize IBI3009; however, the two companies will jointly focus on the early stage development of the candidate. After early stage development, Roche will take over full development. Innovent, in turn, will receive an upfront payment of $80 million and is eligible to receive up to $1 billion in development and commercial milestone payments. Innovent is also eligible to receive tiered royalties on net sales.

“We are delighted to once again enter a strategic collaboration with Roche, a global leader in oncology, to advance our potentially best-in-class DLL3 ADC candidate. By combining Roche's scientific expertise and global development capabilities with our innovative approach, we are taking a significant step forward in our mission—to empower patients worldwide with affordable, high-quality biopharmaceuticals,” said Samuel Zhang, PhD, chief business officer, Innovent, in the press release (1).

DLL3 is an antigen with low expression in normal tissues but is significantly overexpressed in certain cancers, particularly SCLC and other neuroendocrine tumors, making it an attractive target for emerging therapy development (2). IBI3009 has already received investigational new drug (IND) approvals in the United States, China, and Australia and is currently in a Phase I study.

IBI3009 was developed using Innovent’s proprietary novel topoisomerase 1 inhibitor (TOPO1i) platform. It has shown positive anti-tumor activity in multiple tumor-bearing mouse models, particularly chemo-resistant tumor types. The ADC has also demonstrated a favorable safety profile, according to the company press release.

“We are excited to enter this partnership with the Innovent team to further develop this promising investigational treatment for patients with small cell lung cancer. This partnership builds on Roche’s long history of innovation in the area of ADCs, to address the unmet needs of patients with solid tumors with transformational medicines,” said Boris L. Zaïtra, head of Corporate Business Development, Roche, in the release.

Innovent has four new drug applications under regulatory review, and the company’s pipeline includes three assets in Phase III or pivotal clinical trials with 17 more molecules in early clinical stage. Innovent’s global partners include Eli Lilly and Company, Sanofi, Incyte, Adimab, LG Chem, and MD Anderson Cancer Center.

1. Innovent Biologics. Innovent Enters into Exclusive Global License Agreement with Roche for Novel DLL3 Antibody Drug Conjugate. Press Release. Jan. 2, 2025.
2. Rudin, C. M.; Reck, M.; Johnson, M. L.; et al. Emerging Therapies Targeting the Delta-like Ligand 3 (DLL3) in Small Cell Lung Cancer. 

Under the agreement, the companies will advance development of IBI3009, Innovent’s ADC candidate, which has received IND approvals in the US, China, and Australia.

Roche Forms Partnership Worth Potentially More than $1 Billion with Innovent to Develop Novel ADC for SCLC

on Dec. 31, 2024, FDA announced the reopening of the comment period for the 

 notice (FRN), “Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-on Recombinant Peptide Products: Establishment of a Public Docket: Request for Information and Comments”, published on July 25, 2024 (89 

 60436) (2). The comment period has been reopened due to high interest from the industry for the FRN. The comment period will remain open until March 3, 2025 (1).

The December 31 notice establishes a public docket under which substantive comments from interested parties can be submitted on evaluating the immunogenicity risk of host cell proteins (HCPs) in follow-on peptide products. FDA is specifically interested in comments that address suitable methods to detect, identify, and control HCPs in commercial lots of recombinant peptide products (including information on achievable residual amounts of HCPs in the drug product) as well as 

 immunogenicity assessment (IVISIA) of host cell proteins in recombinant peptide products.

Comments can be submitted electronically or in writing. If sent electronically, comments, including any attachments, should be submitted to the Federal eRulemaking Portal at 

. Comments and any accompanying attachments will be posted to the docket unchanged, according to FDA. “Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov,” FDA states in the December 31 notice (1).

Comments that contain confidential information not for public consumption should be submitted as a written/paper submission only.

For written/paper submissions, comments should be submitted by mail, hand delivered, or sent by courier to: Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. For comments submitted in writing, FDA will post the comments, as well as any attachments—except for information submitted that is marked and identified as confidential.

FDA also instructs that all submissions received must include the Docket No. FDA-2024-N-2980 for “Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-On Recombinant Peptide Products; Request for Information and Comments.”

Written/paper submissions that are confidential should be submitted in two copies, with one copy including the information marked as confidential. FDA recommends using a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” The agency will review this copy, including the claimed confidential information, in its consideration of comments, while the second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov.

“Although follow-on recombinant peptide products can rely on FDA’s findings of safety and effectiveness for a listed drug that is a peptide product, differences in recombinant expression systems used during the peptide production could result in quality attribute differences, including in the host cell protein profile, which in turn, could contribute to differences in immunogenicity risk between a follow-on peptide product and the relied upon listed drug,” FDA states in its announcement. Public comments will help the agency develop recommendations for evaluating and mitigating the immunogenicity risk associated with differences in HCP profiles between the follow-on and listed drug.

For more information about the open docket, including what information to include when submitting comments, see the 

Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-On Recombinant Peptide Products; Reopening of the Comment Period

Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-On Recombinant Peptide Products; Establishment of a Public Docket; Request for Information and Comments

The comment period for the Federal Register Notice, “Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-on Recombinant Peptide Products: Establishment of a Public Docket: Request for Information and Comments”, has been reopened by FDA until March 3, 2025.

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