Feliza Mirasol is the science editor for 

Feliza Mirasol

Lonza and Acumen Pharmaceuticals, a clinical-stage biopharmaceutical company specializing in therapeutics that target toxic soluble amyloid beta oligomers (AβOs) for treating Alzheimer’s disease (AD), have formed a collaboration for Lonza to manufacture sabirnetug (ACU193), a monoclonal antibody (mAb) that targets toxic soluble AβOs. Sabirnetug is in clinical development for treating AD and will soon be entering Phase II studies, the companies announced in an April 4, 2024 press release.

Under the agreement, Lonza will manufacture sabirnetug drug substance at its manufacturing facility in Portsmouth, NH. The Portsmouth facility is equipped with 2000-L single-use bioreactors.

“Our collaboration with Acumen showcases our flexibility in enabling innovative biotech companies to advance their innovative therapies on accelerated timelines. We are excited that our new, next-generation single-use manufacturing facility in Portsmouth (US) will be used to manufacture a [C]GMP [current good manufacturing practice] drug substance that could bring new treatment options to patients suffering from Alzheimer’s disease,” said Stefan Egli, global head of Mammalian Biologics, Lonza, in a company press release.

According to the press release, sabirnetug is the first humanized mAb to demonstrate selective target engagement of AβOs in a Phase I first-in-human study. AβOs are known to be an early trigger and persistent driver of AD-associated synaptic dysfunction and neurodegeneration. Sabirnetug operates by preventing toxic AβOs from binding to dendritic spines and by preserving neuronal function, thus addressing an underlying cause of AD, according to the release.

“As we progress into Phase [II] clinical development of sabirnetug as a potentially best-in-class treatment for early AD, we are acutely aware that patients and their families are in urgent need of safe, effective treatment options for this devastating disease. Partnering with Lonza is a critical step to ensure broader access to next-generation AD therapies,” said James Doherty, president and chief development officer, Acumen Pharmaceuticals, in the release.

Regulatory support for the development of AD therapeutics was further advanced this year with the issuance of FDA’s 

 on early AD treatment in March 2024 (1). The guidance document is intended to aid sponsors who are in the clinical phases of developing therapeutics for treating the early stages of AD before dementia becomes overt. The March 2024 draft guidance is a revision of the February 2018 guidance; the draft remains open for comments until June 10, 2024.

In the past, enrollment in clinical trials for AD treatments were based on clinical criteria that defined the later stages of AD, and because of this, study subjects “exhibited both the cognitive changes typical of clinically evident AD and the degree of functional impairment associated with overt dementia,” according to FDA’s guidance document. Approved treatments were thus based on that context. However, FDA expects the new draft document to create discussions between the Office of Neuroscience in the Center for Drug Evaluation and Research, the Office of Therapeutic Products in the Center for Biologics Evaluation and Research, sponsors, the scientific community, and the public, where appropriate (1,2).

Draft Guidance for Industry, Early Alzheimer’s Disease: Developing Drugs for Treatment

 (CBER, CDER, March 2024).
2. Haigney, S. 

FDA Gives Guidance on Developing Treatments for Early Alzheimer’s

Articles

Under a collaboration agreement, Lonza will manufacture sabirnetug, Acumen Pharmaceuticals' mAb in clinical development for treating Alzheimer’s disease.

Lonza Forms Agreement to Manufacture Acumen Pharmaceuticals’ AD mAb Therapy 

In a deal expected to close in the first half of 2024, Genmab will acquire clinical-stage biotechnology company ProfoundBio for $1.8 billion in an all-cash transaction, according to an April 3, 2024 press release. ProfoundBio specializes in developing next-generation antibody drug conjugates (ADCs) and ADC technologies for certain cancers, such as ovarian cancer and other folate receptor alpha (FRα)-expressing solid tumors.  

Under the deal, Genmab will gain worldwide rights to ProfoundBio’s portfolio of next-generation ADCs, which includes three clinical programs and multiple preclinical programs. Clinical programs include Rina-S, a FRα-targeted, topoisomerase 1 (Topo1) ADC currently in the Phase II stage of a Phase I/II clinical trial. Rina-S is being evaluated for treating ovarian cancer and other FRα-expressing solid tumors.

The acquisition will also combine ProfoundBio’s ADC technology platforms with Genmab’s proprietary antibody platforms, potentially creating new opportunities to generate and develop new oncology therapeutics. 

Jan van de Winkel, president and CEO, Genmab. Image courtesy of Genmab.

“The proposed acquisition of ProfoundBio firmly aligns with our long-term strategy and our ambitious 2030 vision to impact the lives of patients through innovative antibody medicines,” said Jan van de Winkel, president and CEO, Genmab, in a company press release. “We believe that ProfoundBio’s ADC candidates, proprietary technology platforms, and talented team will be a great addition to Genmab and that, together, we will be able to accelerate the development of innovative, differentiated antibody therapies for cancer patients.”

The addition of Rina-S to Genmab’s portfolio will additionally strengthen the company’s presence in gynecologic oncology and allow it to build a foundation in solid tumors. This would be possible because Rina-S aims to address a broader patient population than first-generation FRα-targeted ADCs. Based on data from the ongoing Phase I/II clinical trial, Genmab will aim to expand development plans for Rina-S within the ovarian cancer space as well as with other FRα-expressing solid tumors. Rina-S was granted fast track designation by FDA in January 2024 for treating patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.

“Genmab shares our team’s mission of developing novel therapies to improve outcomes for cancer patients. Genmab’s deep expertise in antibody drug development and commercialization makes this a compelling union that will allow us to rapidly develop and realize the full potential of our ADC therapies to benefit patients,” said Baiteng Zhao, ProfoundBio’s co-founder, CEO, and chairman of the board, in the press release.

In recent months, major biopharma players have also made significant moves toward building up ADC capabilities. In December 2023, 

 formed an $8.4 billion collaboration with SystImmune to co-develop and co-commercialize lead ADC candidate for cancer treatment in United States (1). In March 2024, 

 completed its $2 billion acquisition of Ambrx Biopharma, a clinical-stage biopharmaceutical company, which gives J&J the opportunity to design, develop, and commercialize targeted ADCs with Ambrx’s proprietary ADC technology platform. The platform utilizes highly specific-targeting monoclonal antibodies with a potent chemotherapeutic payload (2).

1. Bristol Myers Squibb. SystImmune and Bristol Myers Squibb Announce a Global Strategic Collaboration Agreement for the Development and Commercialization of BL-B01D1. Press Release, Dec. 11, 2023.
2. Johnson & Johnson. Johnson & Johnson Completes Acquisition of Ambrx. Press Release, March 7, 2024.

Genmab's acquisition of ProfoundBio will boost its clinical and preclinical pipeline of ADCs for targeted cancer treatment.

Genmab Expands ADC Pipeline with $1.8 Billion Acquisition of ProfoundBio

FDA granted Johnson & Johnson (J&J) fast track designation on March 26, 2024 for nipocalimab to reduce the risk of fetal neonatal alloimmune thrombocytopenia (FNAIT) in alloimmunizeda pregnant adults during a current pregnancy. Nipocalimab is a high-affinity, fully human, aglycosylated, effectorless, monoclonal antibody (mAb), which, according to AstraZeneca in a company press release, is the only investigational therapy in clinical development to address this indication. Nipocalimab was earlier granted orphan drug designation by FDA for the FNAIT indication in December 2023.

The mAb aims to selectively block the neonatal crystallizable fragment receptor (FcRn), and in doing so, reduce the levels of circulating immunoglobulin G (IgG) antibodies, including autoantibodies and alloantibodies that underlie multiple conditions, J&J stated in its press release. According to the company, “Nipocalimab is the only FcRn blocker being studied across three key segments in the autoantibody space: rare autoantibody diseases (e.g., generalized myasthenia gravis in adults and children, chronic inflammatory demyelinating polyneuropathy, warm autoimmune hemolytic anemia, and idiopathic inflammatory myopathies); maternal fetal diseases mediated by maternal alloantibodies (e.g., hemolytic disease of the fetus and newborn and fetal and neonatal alloimmune thrombocytopenia); and prevalent rheumatology (e.g., rheumatoid arthritis, Sjögren’s disease, and systemic lupus erythematosus).”

FNAIT is a severe and rare condition. It occurs when the pregnant person’s immune system mistakenly attacks a developing fetus’ platelets, which can impair clotting ability and lead to internal bleeding, which poses a significant risk to the fetus or newborn. Blocking FcRn can potentially reduce overall IgG levels, including pathogenic alloantibody levels. At the same time, the blockage can preserve immune function without causing immunosuppression on a broader scale. Blocking IgG from binding to FcRn in the placenta may also potentially prevent the transfer of maternal alloantibodies to the fetus, according to the press release.

“Receiving [f]ast [t]rack designation for nipocalimab in FNAIT underscores the urgency to address the unmet need for safe, effective, and targeted treatments to prevent FNAIT, a condition that could carry severe health consequences and even be fatal for the fetus or newborn,” said Katie Abouzahr, vice-president, Autoantibody and Maternal Fetal Immunology Disease Area Leader, Johnson & Johnson, in the release. “We are committed to applying our decades of immunology leadership to pioneer innovative approaches to transform treatment for patients and their families affected by FNAIT and other alloantibody-driven diseases of pregnancy.”

Nipocalimab is also being studied for treating hemolytic disease of fetus and newborn (HDFN), another alloimmune disease related to pregnancy. HDFN has a similar disease mechanism as FNAIT and is often referred to as the red-blood-cell-counterpart to FNAIT. J&J will proceed with Phase III trials focused on HDFN following safety and efficacy results from a Phase II trial.

The rare disease sector is currently a major focus of big biopharmaceutical companies. For instance, earlier this year in January 2024, 

 made a move to acquire Inhibrx, a clinical-stage biopharmaceutical company. The deal is valued at approximately $1.7 billion (1). Among the assets Sanofi will gain is INBRX-101, a human recombinant protein that can potentially normalize serum alpha-1-antitrypsin (AAT) levels in patients that are AAT deficient. AAT deficiency is a rare genetic disease that is defined by low levels of AAT protein. Symptoms primarily affect the lungs, and there is a progressive deterioration of the tissue.

In addition, AstraZeneca recently received FDA approval for its 

, Ultomiris (ravulizumab-cwvz). FDA approved Ultomiris on March 25, 2024 for treating adult patients with anti-aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum disorder (NMOSD) in the United States (2). NMOSD is a rare and debilitating autoimmune disease that affects the central nervous system, including the spine and optic nerves.

1. Sanofi. Sanofi to Acquire Inhibrx, Inc., Adding Potential Best-In-Class Rare Disease Asset for Alpha-1 Antitrypsin Deficiency to Pipeline. Press Release, Jan. 23, 2024.
2. AstraZeneca. Ultomiris Approved in the US for the Treatment of Adults with Neuromyelitis Optica Spectrum Disorder (NMOSD). Press Release, March 25, 2024.

FDA granted fast track designation to nipocalimab, which J&J is developing for helping alloimmunized pregnant adults treat FNAIT, a rare disease that poses risk to the fetus or newborn.

J&J's Nipocalimab for FNAIT Gets on Fast Track for Approval

FDA has approved Ultomiris (ravulizumab-cwvz), making it the first and only long-acting C5 complement inhibitor in the United States for treating adult patients with anti-aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum disorder (NMOSD). AstraZeneca announced the approval on March 25, 2024.

The approval was based on positive results from a Phase III trial (CHAMPION-NMOSD) that showed Ultomiris met the primary endpoint of time to first on-trial relapse. Zero relapses were observed among patients treated with Ultomiris. The median treatment duration was 73 weeks with a relapse risk reduction of 98.6%.

Sean J. Pittock, the director of the Mayo Clinic's Center for Multiple Sclerosis and Autoimmune Neurology and of Mayo's Neuroimmunology Laboratory and lead primary investigator in the Phase III trial, said in the press release that, “C5 inhibition has been proven to offer efficacy in reducing the risk of NMOSD relapses by blocking the complement system, a part of the immune system, from attacking healthy cells in the spinal cord, optic nerve, and brain. With today’s FDA approval, patients now have the option of a long-acting C5 inhibitor treatment that showed zero relapses in the pivotal CHAMPION-NMOSD trial, supporting the primary goal of relapse prevention in treating NMOSD.” 

Sean J. Pittock, MD, director, Center for Multiple Sclerosis and Autoimmune Neurology and Neuroimmunology Laboratory, Mayo Clinic. Lead primary investigator in the CHAMPION-NMOSD trial. Image courtesy of Mayo Clinic.

Ultomiris is also approved for certain adults with NMOSD in Japan and the European Union, while regulatory reviews in additional countries remain ongoing.

NMOSD is known to be a rare and debilitating autoimmune disease. It affects the central nervous system, including the spine and optic nerves. Most people living with the disease experience unpredictable relapses, which involve a new onset of neurologic symptoms or the worsening of existing neurologic symptoms. These relapses tend to be severe and recurrent and carry the risk of causing permanent disability. Approximately 6000 adults in the US are estimated to be affected by NMOSD, according to AstraZeneca in the press release.

“Alexion has been at the forefront of innovation in NMOSD, striving to offer patients a future without fear of life-altering or even fatal relapses. Building on the established efficacy of C5 inhibition for people living with AQP4 Ab+ NMOSD, we are proud to deliver a transformative, long-acting treatment option that has the potential to eliminate relapses with a convenient dosing schedule every eight weeks. We are grateful to the NMOSD community for their ongoing collaboration and input, which enables us to advance science for rare diseases,” said Marc Dunoyer, chief executive officer, Alexion, the group within AstraZeneca focused on rare diseases, in the press release.

The rare disease group was created following the completion of AstraZeneca’s approximately $13.3 billion acquisition of Alexion Pharmaceuticals in 2021 (1). With the acquisition, AstraZeneca strengthened its scientific presence in immunology, allowing the company to address the significant unmet medical need in the rare diseases sector. Alexion’s focus is on research in novel molecules aimed toward development of therapeutics for hematology, nephrology, neurology, metabolic disorders, cardiology, and ophthalmology.

1. AstraZeneca. Acquisition of Alexion Completed. Press Release, July 21, 2021.

FDA has approved AstraZeneca's Ultomiris, marking the first and only long-acting C5 complement inhibitor for patients with NMOSD.

AstraZeneca Gains FDA Nod for Ultomiris, a Treatment for Managing NMOSD

AbbVie has entered into a definitive agreement to acquire Landos Biopharma, a clinical-stage biopharmaceutical company focusing on autoimmune diseases, following an earlier approval of ELAHERE (mirvetuximab soravtansine-gynx), a new antibody-drug conjugate (ADC) for treating ovarian cancer, by FDA, the company announced on March 25, 2024.

Under the Landos agreement, AbbVie will acquire Landos for $20.42 per share, an aggregate value of approximately $137.5 million, in cash upon closing. The deal also includes one non-tradable contingent value right per share at a value of up to $11.14 per share (approximately an additional $75 million in aggregate), dependent on achieving a clinical development milestone. The transaction is expected to close in the second quarter of 2024

The Landos acquisition includes a lead asset, NX-13, an oral nucleotide oligomerization domain-like receptor family member X1 (NLRX1) agonist with a bimodal mechanism of action (MOA) that is anti-inflammatory and that facilitates epithelial repair. NX-13 is in a Phase II clinical trial (NEXUS ) in the United States and Europe for treating ulcerative colitis (UC). According to AbbVie in a company press release, “NLRX1 regulates immunometabolism and inflammation, and its activation impacts multiple mechanisms of inflammatory bowel disease (IBD) pathogenesis.”

"This announcement is a testament to Landos' talented team and their commitment to our mission of creating oral treatments that can address a therapeutic gap," said Gregory Oakes, president and chief executive officer, Landos, in the press release. "NX-13 and its bimodal MOA have the potential to provide a novel approach to the treatment of ulcerative colitis and Crohn's disease. With AbbVie's therapeutic area leadership and expertise in global development, they are the right company to further advance NX-13."

The March 22, 2024 full approval granted by FDA for ELAHERE, meanwhile, advances the field of ADC therapeutics. ELAHERE is now indicated for treating adult patients with folate receptor-alpha (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. The indication is specifically for those patients who have received one to three prior systemic treatment regimens.

, which came to AbbVie with its acquisition of ImmunoGen in February 2024 (1), was first granted 

 by FDA in November 2022 (2). Full approval was based on a confirmatory Phase III trial (MIRASOL), whose data showed that treatment with ELAHERE resulted in an overall survival benefit and a reduced risk of cancer progression by 35%, according to a company press release.

"The full FDA approval of ELAHERE for eligible patients with ovarian cancer represents the culmination of years of work by the ImmunoGen team. ELAHERE is the first and only antibody-drug conjugate (ADC) approved in the US for this difficult-to-treat malignancy," said Roopal Thakkar, senior vice-president, chief medical officer, global therapeutics, AbbVie, in the press release

"As the first treatment to show a statistically significant overall survival benefit in patients with platinum-resistant ovarian cancer, ELAHERE provides an effective new option for patients with folate receptor alpha positive tumors. These patients previously had very limited options and ELAHERE changes that," said Kathleen Moore, deputy director and associate director of clinical research at the Stephenson Cancer Center of The University of Oklahoma and MIRASOL principal investigator.

A marketing authorization application for the ADC in Europe has been accepted by the European Medicines Agency, and regulatory submissions are also under review in multiple other countries.

1. AbbVie. AbbVie Completes Acquisition of ImmunoGen. Press Release, Feb. 12, 2024.
2. FDA. 

FDA Grants Accelerated Approval to Mirvetuximab Soravtansine-Gynx for FRα Positive, Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer

The Landos acquisition adds a lead asset in autoimmune and inflammatory disease to AbbVie's portfolio, while the company's ADC, ELAHERE, gets full FDA approval. 

AbbVie Gains Landos Biopharma and Full FDA Approval for ADC Product

Editor's note: this story was originally published in BioPharmInternational.com.

Roche has entered into an agreement to sell its large-scale biologics manufacturing site in Vacaville, Calif., to Lonza for $1.2 billion, Lonza announced on March 20, 2024. Lonza plans to invest approximately CHF 500 million (US$557 million) to upgrade the facility and enhance capabilities at the site for next-generation mammalian biologics.

The deal is expected to close in the second half of 2024, subject to customary closing conditions. The Vacaville site will be integrated into Lonza’s Biologics division upon closing and will be included in Lonza’s network of existing mammalian manufacturing sites in Visp, Switzerland; Slough, United Kingdom; Tuas, Singapore; Portsmouth, NH; and Porriño, Spain (1).

“The Vacaville site is a highly valuable strategic acquisition that will make capacity immediately available for our customers and unlock future growth for our Biologics division. It will support us in providing a commercialization path to existing customers and incremental large-scale commercial capacity to our partners,” said Jean-Christophe Hyvert, president, Biologics, Lonza, in a company press release.

Lonza will supply the products currently manufactured by Roche at the Vacaville site in the medium term as it phases out those products over time to serve alternative customers. With a total bioreactor capacity of approximately 330,000 L, Lonza expects the Vacaville acquisition to significantly increase its large-scale biologics manufacturing capacity, allowing it to meet demand for commercial mammalian contract manufacturing from customers with existing commercial products. The facility will also serve molecules within Lonza’s network that are currently on the path to commercialization.

The facility’s capacity makes it one of the largest biologics manufacturing sites in the world by volume, according to the Lonza company press release. Because demand for commercial-scale capacity for biologics is expected to remain high across the contract development and manufacturing organization industry as the result of anticipated approvals for innovative new therapies, the acquisition puts Lonza in a position to offer immediate access to significant new capacity in the United States. The move also creates a significant West Coast commercial manufacturing presence, which complements Lonza’s existing biologics site on the East Coast (Portsmouth, NH). The US sites also complement Lonza’s manufacturing network across Europe and Asia.

“Demand for biologics manufacturing capacity by volume is projected to reach nearly 4400 kL, a five-year growth rate of nearly 11.5% per year (just over 2500 kL in 2022). Global biologics manufacturing capacity will increase to nearly 8400 kL by 2027 from nearly 6500 kL in 2023,” according to the 2023 CPHI annual report (2).

“We have deep and long-standing industrial expertise in delivering commercial-scale manufacturing services for our customers’ therapies. In combining this with the strong legacy of the Vacaville facility, its highly skilled colleague community, and its proven track record on quality, we are excited to take our leading large-scale mammalian offering to its next chapter of growth,” Hyvert said in the press release.

Under the transaction, Lonza will offer positions to the approximately 750 Genentech employees working at the Vacaville facility.

1. Lonza. Mammalian Biopharmaceutical Services. 

 (accessed March 25, 2024).
2. Ecker, D. M.; Seymour, P. Supply and Demand Trends: 2022-2027 Mammalian Biomanufacturing Industry Overview. In 

The Vacaville, Calif., site acquisition gives Lonza one of the largest biologics manufacturing sites for mammalian cell-based therapies worldwide.