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Monoclonal antibodies are engineered proteins that act like human antibodies in the immune system. They are a kind of targeted drug therapy that are mainly used to treat cancer and conditions that affect immune cells.
The first monoclonal antibody, muromonab-CD3, was approved nearly 40 years ago to suppress an overactive immune system in patients who received organ transplants, so as to treat organ rejection.
Since then, the U.S. Food and Drug Administration (FDA) has approved well over a hundred monoclonal antibodies to treat a range of diseases.
In this article, let us take a look at eight biotech companies dedicated to advancing their monoclonal antibodies through the clinic, and that have made the news in recent times.
Table of contents
Arcus Biosciences
Committed to treating cancer, American biotech company Arcus Biosciences has created a portfolio of drugs that are made up of monoclonal antibodies and small molecules.
Its candidate domvanalimab is a monoclonal antibody that works by binding to TIGIT, which could activate the immune system to attack cancer cells. Typically, a fragment crystallizable (Fc) region in a monoclonal antibody, which is at the tail end of the antibody, interacts with receptors and binds to them, and then activates immune cells. This tends to cause antibody-dependent cellular cytotoxicity (ADCC) and in turn, the depletion of certain immune cells like regulatory T cells crucial for antitumor activity.
Arcus’ domvanalimab has a silent Fc domain instead, which does not interact with the receptors and, therefore, retains the regulatory T cells in the system. Domvanalimab is being used in combination with zimberelimab, a monoclonal antibody that binds to PD1 in cancer cells. Together, the anticancer response is strengthened. The drug combination is currently in phase 3 trials to treat lung cancer and gastrointestinal cancer.
In January, the biopharma received $320 million from Gilead as the two have made plans to accelerate the domvanalimab program, for which they discontinued a trial for non-small cell lung cancer (NSCLC) citing that they want to “address a higher unmet need for patients with lung and gastrointestinal cancers.”
Astria Therapeutics
Situated in the biotech hub of Boston, Massachusetts, Astria Therapeutics is committed to combating allergic and immunological diseases with its two monoclonal antibodies in the making.
Its lead candidate STAR-021 inhibits plasma kallikrein to hereditary angioedema (HAE). The disease is caused by either the lack of or the presence of a dysfunctional C1-inhibitor protein, which leads to symptoms like abdominal pain, nausea, and vomiting. An HAE attack can result in rapid swelling of the hands, feet, limbs, face, intestinal tract, voicebox, and windpipe.
Recently, the biotech announced positive initial proof-of-concept results from a phase 1b/2 trial. The drug reduced monthly attack rates by 90-96% in patients, and was well-tolerated. This gives way to a phase 3 study, which will begin next year.
Astria’s other candidate STAR-0310 is an OX40 antagonist, meaning that it blocks the receptor OX40, which is expressed in T cells in the case of atopic dermatitis – the most common form of eczema where the skin becomes itchy, dry, and cracked. STAR-0310 is currently undergoing preclinical studies, and Astria aims to submit an Investigational New Drug (IND) application by the end of this year for the drug to enter the clinic.
In January, the biotech raised $125 million.
BioArctic
On a mission to advance its robust pipeline that includes Alzheimer’s drug lecanemab, which was approved by the FDA last year, Swedish biotech BioArctic is focused on treating neurodegenerative conditions.
It partnered with Japanese biopharma Eisai to bring lecanemab, sold under the brand name Leqembi, into the market. So far, the drug has reaped JPY 2.83 billion ($18.14 million) in revenues this year.
The company’s monoclonal antibody targets the buildup of amyloid plaques in the brain, a hallmark of Alzheimer’s disease. It is being tested in a phase 3 study with people who have Alzheimer’s but don’t show the symptoms yet, and a refined version of the drug is in preclinical trials.
Another neurodegenerative disease that BioArctic looks to counter is Parkinson’s disease. Its phase 1 candidate exidavenmab is a monoclonal antibody that binds to toxic forms of alpha-synuclein – a protein that can cause inflammation in the brain – to slow disease progression. The drug will soon enter phase 2 trials.
The biotech’s BrainTransporter technology aids antibodies to pass through the blood brain barrier. The barrier protects the brain from harmful substances but also tends to stall the entry of larger molecules like antibodies, making it harder for drug delivery.
HiFiBiO Therapeutics
Named one of Fierce Biotech’s Fierce 15 of 2023, HiFiBiO Therapeutics is an immunotherapy company that has operations in the U.S., France, China, and Hong Kong. Its pipeline consists of a range of drugs in preclinical and clinical development.
The most advanced candidate is HFB200301, which targets the TNFR2 receptor that is expressed on regulatory T cells. Binding to TNFR2 activates CD4 and CD8 T cells, and is able to demonstrate antitumor activity in cancer cells.
Having received IND clearance in 2021, a phase 1 dose escalation study for HFB200301 is underway for treating solid tumors. The drug is also being tested in combination with humanized monoclonal antibody tislelizumab.
Moreover, the drug has also been designed to target OX-40, and is being evaluated in another phase 1 trial against solid tumors.
But cancer is not the only indication that the biotech aims to treat. Its preclinical candidate HFB200604 for autoimmune diseases targets BTLA, an inhibitory immune checkpoint expressed on B and T cells.
Last month, HiFiBiO was awarded a grant by the Patient-Led Research Fund to research long COVID in collaboration with UMass Chan Medical School in the U.S.
Invivyd
U.S.-based Invivyd, which was founded in the early days of the pandemic, is known for its COVID-19 drug Pemivibart, which was granted emergency use by the FDA in March.
Pemivibart is a monoclonal antibody that is used to prevent COVID-19 infections in adolescents and adults whose immune systems have been compromised by other medical conditions or immunosuppressive drugs. The drug targets the spike protein found in coronavirus, which gives the pathogen its crown-like appearance and causes inflammation in the host body.
Meanwhile, a phase 3 trial for its other monoclonal antibody VYD222 is underway to treat symptomatic COVID-19. VYD222 was engineered from Invivyd’s investigational monoclonal antibody adintrevimab. According to initial results of the ongoing study, the drug produced high serum virus neutralizing antibody titer levels in patients who have weak immune systems (immunocompromised), and was found to be safe.
Renaissance Pharma
Focused on treating children with rare diseases, British biotech Renaissance Pharma is pushing ahead with its lead candidate Hu14.18K322A for neuroblastoma.
Neuroblastoma is a type of cancer that forms in nerve cells that aren’t fully formed. It is the most common form of cancer in infants, and around 700 to 800 children are diagnosed in the U.S. every year.
The company’s Hu14.18K322A is a humanized, anti-GD2 monoclonal antibody that latches onto the surface of neuroblastoma tumor cells. The binding prompts immune cells to kill tumor cells.
In a phase 2 study in high-risk children, the drug had an overall survival rate of 86% when combined with chemotherapy. All the patients showed clinical benefit as well. These results seem particularly encouraging as almost half of all patients with newly-diagnosed high-risk neuroblastoma do not survive despite various other treatments.
Last month, Renaissance was bought by Essential Pharma to drive Hu14.18K322A’s journey through the clinic.
SynOx Therapeutics
Based in Ireland and the U.K., clinical-stage SynOx Therapeutics is en route to treat tenosynovial giant cell tumor (TGCT).
While most often TGCT is a benign group of tumors that grow in the synovial lining of joint and tendon sheaths – found in the knee, hip, and ankle – sometimes, they can become aggressive. They form when colony stimulating factor 1 (CSF-1) is secreted in excess, typically due to a chromosome abnormality. CSF-1 triggers the movement of tumor-associated macrophages (TAMs) to tumor sites, which in turn, suppress immune responses.
Although surgery is the primary treatment approach for TGCT, sometimes, because of the tumor’s size and location in a joint, surgery could damage the lining of the joint, calling for other treatment approaches.
The company’s phase 3 candidate emactuzumab is a monoclonal antibody that can halt CSF-1 production, thereby evoking an anti-tumor immune response. In the clinic, the drug had a 70% overall response rate (ORR) after a year, and a 64% ORR after two years.
Two days ago, it said that it secured a $35 million loan to further develop and eventually commercialize emactuzumab. Last month, it also pocketed $75 million in a series B funding round.
Vaccinex
American biopharma company Vaccinex is devoted to cancer and neurologic diseases with the help of its lead candidate monoclonal antibody pepinemab.
The drug inhibits semaphorin 4D (SEMA4D), a protein that can induce myeloid suppressor cells in tumors and trigger neuroinflammation in the brain. Pepinemab is designed to increase immune activity against tumors and regulate normal brain function in Alzheimer’s and Huntington’s disease.
It recently completed a phase 2 study for Huntington’s, and a phase 2 study is ongoing for Azheimer’s disease. In head and neck cancer, interim phase 2 data showed that when the drug was given with immunotherapy drug Keytruda, ORR doubled, and so did the progression free survival of patients.
In March, Vaccinex obtained $1.5 million in a registered direct offering and a private investment in public equity (PIPE) deal.
Monoclonal antibodies: an expanding therapeutic field
The monoclonal antibodies market was valued at 210 billion in 2022, and is projected to increase by 11% every year until 2030. Pharma giants like Johnson & Johnson and Bristol-Myers Squibb have been key players, having played a part in these growing revenues. Multinational biopharma company Regeneron also has over 25 monoclonal antibodies in various stages of clinical development to address conditions ranging from anemia and metabolic diseases to cancer, inflammatory diseases, and rare diseases.
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