Feliza Mirasol is the science editor for 

Feliza Mirasol

FDA has granted fast track designation to Johnson & Johnson (J&J) for posdinemab, an investigational phosphorylated tau-directed monoclonal antibody (mAb) for treating patients with early Alzheimer’s disease (AD), J&J announced on Jan. 8, 2025. Discovered by J&J, posdinemab is in a Phase IIb study (AuTonomy) and has shown potential in targeting disease-associated phosphorylated tau in cerebrospinal fluid (CSF) from AD patients who are being treated. The mAb has also shown an ability to block the development and spread of tau aggregates in non-clinical models of disease.

FDA’s decision on posdinemab marks the second fast track designation granted to J&J in 2024 for its AD portfolio. In July 2024, FDA granted fast track designation to J&J’s anti-tau active immunotherapy, JNJ-2056, which represents the first active immunotherapy that targets tau in a preclinical AD population (1). JNJ-2056 is in a Phase IIb trial (ReTain), which is currently actively enrolling patients. This Phase IIb trial will evaluate the potential of JNJ-2056 to activate the immune system so that it generates antibodies against pathological phosphorylated tau. The goal with this mode of action is to delay or prevent the onset of AD symptoms and, ultimately, progression of the disease.

“As the average age of the global population increases, the number of people impacted by this debilitating progressive disease continues to rise. Alzheimer’s disease places a substantial emotional and financial burden on patients and their loved ones and has a significant economic and societal impact. At J&J, we envision a future where we can help stop the progression of AD the moment it’s detected,” said Bill Martin, PhD, global therapeutic area head, Neuroscience, Johnson & Johnson Innovative Medicine, in a company press release (1).

Posdinemab targets the mid-domain of AD-specific phosphorylated tau. The mAb is designed to bind to pathological phosphorylated tau when released from neurons and to neutralize it before it can seed or spread to another neuron. Tau, which is abundant in neurons, has a notorious reputation, which is due to the fact that it is found deposited in cells as fibrillar lesions in many neurodegenerative diseases, especially AD (2). Posdinemab has shown promise in reducing tau seeding, which is the process by which toxic tau spreads through the brain, in both 

“Posdinemab has the potential to slow the spread of tau pathology in the brain—which may slow cognitive decline. [FDA’s] [f]ast [t]rack designation reflects the urgent unmet need for new treatment options for the millions living with AD,” said Martin in the press release.

Meanwhile, JNJ-2056 (formerly ACI-35.030, in collaboration with AC Immune) is an investigational anti-tau active immunotherapy that targets the c-terminal region of pathological phosphorylated tau. This therapy is designed to inhibit the seeding and spreading of pathological tau as well, also with the goal of delaying or preventing the onset of clinical symptoms in preclinical AD. The Phase IIb in which JNJ-2056 is being evaluated includes participants with preclinical AD who have tau pathology in their brains but have not yet developed cognitive impairment.

Johnson & Johnson’s Posdinemab and Tau Active Immunotherapy Receive US FDA Fast Track Designations for the Treatment of Alzheimer’s Disease

. Press Release. Jan. 8, 2025.
2. Stoothoff, W. H.; Johnson, G. V. W. Tau Phosphorylation: Physiological and Pathological Consequences. 

Biochimica et Biophysica Acta (BBA)—Molecular Basis of Disease

 (2–3), 280-297. DOI: 10.1016/j.bbadis.2004.06.017

Articles

Posdinemab is the second tau-directed investigational therapy by J&J that has received fast track designation from FDA this year for Alzheimer’s disease.

J&J Gets FDA Fast Track Designation for Alzheimer’s mAb, Posdinemab

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

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

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

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.