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Fusion proteins have long been on the market to treat several diseases, including cancer, autoimmune, and rare conditions. These therapeutic agents have caught the attention of biopharma and investors alike these past months attracting dollars from deep pockets in the pursuit of commercial success.
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Nomlabofusp developer Larimar Therapeutics $69 million public offering
American company Larimar Therapeutics is the latest to raise funds to fuel the clinical development of its prized possession, a fusion protein called nomlabofusp. It closed a $69 million public offering last week to cover research and development (R&D) as well as pre-commercialization costs.
Nomlabofusp is a recombinant fusion protein. These types of proteins are created by fusing two or more genes together through recombinant DNA technology, a process that combines genetic material to produce new DNA sequences. The main goal of creating fusion proteins in drug development is to retain properties from all the proteins that result in the new engineered protein.
Discovered by R. Mark Payne, professor of pediatrics at Indiana University School of Medicine and a pediatric cardiologist at Riley Children’s Health, nomlabofusp works as a protein replacement therapy for Friedreich’s ataxia, a rare, inherited neurodegenerative disorder that affects the nervous system. Affecting one in every 22,000 to 50,000 people, according to a report by Rare Disease Advisor, Friedreich’s ataxia can result in muscle weakness, involuntary jerking, loss of touch, balance, and coordination, fatigue, difficulty swallowing, and even vision loss, among other symptoms. The lack of frataxin in the mitochondria in patients with the neurodegenerative condition is what leads to many of these symptoms.
“My research revolved around how mitochondria make energy and regulate the cell,” said Payne. “As part of this, I studied how proteins get imported into mitochondria, which later became the key to my connection with Friedreich’s ataxia.”
Larimar’s fusion protein is designed to deliver frataxin into the mitochondria to treat the condition. Since disease progression is more rapid in patients with lower frataxin levels, the therapy is aimed at curbing the worsening of symptoms. This was evidenced in a clinical study evaluating the safety and tolerability, pharmacokinetics – how well the body interacts with a drug – and FXN levels in cheek and skin cells.
The fusion protein was given daily via subcutaneous injections at a 25 mg dosage and was well tolerated in 14 participants for up to 260 days. Frataxin levels showed a change from baseline of 1.32 pg/μg in buccal cells and 9.28 pg/μg in skin cells after 90 days. These levels increased and were maintained over time, with mean levels increasing from 15% of healthy volunteers at baseline to 30% in cheek (buccal) cells and from 16% to 72% in skin cells after 90 days.
As more data from the trial is set to be announced next month, Larimar plans to submit the Biologics License Application (BLA) for nomlabofusp next year, and the $69 million funding it received will cover the expenses for the drug’s development until then.
Citius Oncology and Illimis Therapeutics want to expand fusion protein R&D
Also last month, Citius Oncology and Illimis Therapeutics raised millions in funding for their fusion proteins. New Jersey-based Citius Oncology racked up $9 million in a public offering, strengthening “its ability to execute Lymphir’s commercial rollout,” according to Leonard Mazur, CEO of Citius.
The fusion protein Lymphir was greenlit by the U.S. Food and Drug Administration (FDA) to treat T cell lymphoma, a type of blood cancer that develops from abnormal T cells, almost a year ago.
Lymphir is the only FDA-approved immunotherapy of its kind for relapsed or refractory cutaneous T-cell lymphoma, explained Mazur.
By binding to the IL-2 receptor, Lymphir not only delivers its toxin payload to directly kill tumor cells, but it also temporarily depletes immunosuppressive regulatory T-cells called Tregs to unlock the body’s own immune system to help fight the cancer.
“Fusion proteins are reshaping oncology because they offer precision with purpose by directly targeting cancer cells and minimizing the impact on healthy tissue. As the industry moves toward smarter, more targeted therapies, fusion proteins are among the most promising tools in the fight against cancer.”
“This dual mechanism of action sets Lymphir apart from other therapies. With a proven safety profile and a unique mechanism of action, Lymphir offers an effective targeted therapy for a rare disease that has no cure,” Mazur told Labiotech.
Apart from marketing the drug, the money will also go towards the fusion protein’s further development as a cancer therapeutic. It is currently being explored in two investigator-initiated trials, one at the Masonic Cancer Center at the University of Minnesota as a treatment prior to CAR-T therapy in patients with high-risk relapsed or refractory B-cell lymphoma, and the other in combination with the cancer immunotherapy drug Keytruda in patients with solid tumors at the Hillman Cancer Center at the University of Pittsburgh Medical Center.
As for South Korean company Illimis, it raked in KRW 58 billion ($42 million) in a series B financing round in a bid to accelerate its central nervous system-focused pipeline, which consists of fusion proteins. The preclinical-stage biotech’s lead candidate is ILM01, a fusion protein that targets protein fragments called amyloid beta that are the hallmark of Alzheimer’s disease when they accumulate in the brain.
The candidate ILM01, which is in the lead optimization stage, is born from the startup’s Gas6-mediated Anti-Inflammatory Adaptor (GAIA) platform. The bispecific fusion protein mounts the amyloid target on one side, and another receptor called the TAM receptor, involved in immune responses, on the other side. Using this strategy, it helps clear misfolded amyloid proteins by eating them up through a process known as phagocytosis while avoiding inflammation.
“In the evolving landscape of new drug development, where the limitations of existing medications are continually being overcome, Illimis’ differentiated platform technology is expected to emerge as a next-generation treatment option for neuro-immune diseases with high unmet medical needs,” said Yohan Kim, Senior Managing Director at DSC Investment, who led this investment round and has also been appointed to the board of directors, in a recent press release.
While fusion protein-focused developers have been no stranger to gaining funding, June and July has really seen an uptick in these numbers. Citius’ Mazur thinks it is because the industry is moving towards precision medicine, prioritizing safety, especially in cancer care.
“Fusion proteins are reshaping oncology because they offer precision with purpose by directly targeting cancer cells and minimizing the impact on healthy tissue. As the industry moves toward smarter, more targeted therapies, fusion proteins are among the most promising tools in the fight against cancer,” said Mazur.
Fusion protein R&D: Cidara Therapeutics closes public offering and Vor Bio makes a comeback
In June, Cidara Therapeutics and Vor Bio were both awarded funding too. California-based Cidara bagged $402.5 million in a public offering. This was following positive topline results of its phase 2 candidate CD388. It is a drug-Fc conjugate (DFC), which is essentially a new kind of fusion protein that Cidara describes as ‘single molecule cocktails.’ It comprises multiple copies of an antiviral small molecule neuraminidase inhibitor conjugated to a human antibody.
The results from the influenza trial that was followed by the public offering showed that 450 mg, 300 mg, and 150 mg of CD388 led to 76%, 61%, and 58% protection against influenza over 24 weeks compared to placebo, as the trial hit its primary and all secondary efficacy endpoints.
In the case of Massachusetts-based Vor Bio, it not only inked a $4 billion deal with China-based RemeGen to develop and commercialize the fusion protein telitacicept across the globe except in regions such as China, Hong Kong, Macau, and Taiwan, but also pocketed $175 million in a private placement. The autoimmune therapeutics developer has had a bumpy ride since it announced plans to wind down operations in May, having slashed 95% of its workforce.
Now, with more money in hand, it will hold a phase 3 study for telitacicept for myasthenia gravis, a chronic autoimmune neuromuscular disease that causes muscle weakness and fatigue. Telitacicept works by inhibiting two proteins called cytokines that are essential to B cell and plasma cell survival. This, in turn, reduces the production of autoreactive immune cells, which are implicated in autoimmune conditions like myasthenia gravis.
Deals on the rise: big pharma keen on fusion proteins
Vor Bio’s interest in telitacicept is part of a growing trend in partnerships to develop fusion proteins. And it looks like multinational pharma companies have caught wind. BioMarin, for instance, spent around $270 million to get a hold of Massachusetts-based Inozyme’s phase 3 drug INZ-701 in an acquisition deal last month. Trials are ongoing to treat ENPP1 deficiency, a rare, serious, and progressive genetic condition that affects blood vessels, soft tissues, and bones.
People with ENPP1 deficiency have one or two ENPP1 gene mutations, which may cause ENPP1 enzyme activity to be reduced or even absent. INZ-701 functions by replacing the deficient ENPP1, thereby preventing symptoms like the softening of the bones, severe bone pain, and fractures. So, this acquisition will add to BioMarin’s portfolio of enzyme therapies.
Meanwhile, Lilly and BMS have also ramped up their game in the field of fusion proteins. Lilly forged a $650 million pact with California-based Juvena Therapeutics to employ an artificial intelligence (AI)-powered screening platform to map signaling proteins and find out their therapeutic potential.
Juvena’s lead candidate is a fusion protein to address myotonic dystrophy type 1, a genetic disorder characterized by muscle weakness, and sarcopenia – linked to the loss of muscle mass, strength, and function – whereas Lilly has its own cohort of fusion proteins that includes insulin efsitora alfa, its once-weekly slow-acting insulin.
Moreover, pharma giant Bristol Myers Squibb spun out a company, handing over $300 million in funding and five autoimmune disease drugs, one of which is a fusion protein, just last week. The yet-to-be-named startup will own and develop the IL2 fusion protein BMS-986326, which is being tested in phase 1 studies for systemic lupus erythematosus, where the body’s immune system mistakenly attacks healthy tissue and causes organ damage, and the chronic inflammatory skin condition atopic dermatitis.
With more funds attributed to the technological space, further R&D is made possible. Meanwhile, if Larimar’s makes it past the FDA, it would be the first disease-modifying therapy for patients with Friedreich’s ataxia and would join the growing list of fusion proteins approved by regulators.
Immunology & inflammation R&D trends and breakthrough innovations
