With advances in technology, an increasing number of stable peptide-based therapeutics are being brought to market today across a wide range of therapeutic areas. Through expert insight, we explain why the peptide field is generating so much excitement, outline some of the most significant recent breakthroughs and big-ticket investments, and highlight the challenges that remain in the path of its future development.
Peptides are naturally occurring biological molecules consisting of 2-50 amino acids (as opposed to larger chain of >50 amino acids generally referred to as proteins). Because therapeutics based on these molecules can be metabolised by the body, they are seen as relatively safe and well-tolerated.
Peptide-based drugs made up only five percent of the global pharmaceutical market in 2019, but this still accounts for an enormous USD 60 billion total market size. Moreover, new peptide drug approvals have consistently risen over the past 60 years, from only five between 1960 and 1979 to 29 between 1980 and 1999 and 52 between 2000 and 2019 according to Muttenthaler, King & Adams et al’s recent study in Nature. Today, more than 80 peptide drugs have reached the market for diseases ranging from diabetes to cancer, osteoporosis, multiple sclerosis, HIV infection and chronic pain.
Reaching Technological Maturity
One man well placed to comment on the vast potential in the peptide field is Carlo Toniatti of Italian firm IRBM. Once part of MSD as the Merck Peptide Centre of Excellence, IRBM is now an independent contract research organisation (CRO) but has retained its peptide expertise and is currently working with its former parent company on peptide-based therapeutics for COVID-19.
Nowadays, the field has reached technological maturity and peptides’ potential uses as therapeutic agents have hugely increased
Carlo Toniatti, IRBM
“Peptides are a growing field in which interest has fluctuated over the years,” begins Toniatti. “There was a lot of excitement around peptides in the past, but some technological limitations, including, for example, poor pharmacokinetic profiles (i.e., short-half life in the body), and the cost of large-scale manufacturing, resulting in the commercial development of peptides with agonistic activity within a relatively narrow number of therapeutic indications.”
He continues, “Nowadays, the field has reached technological maturity and peptides’ potential uses as therapeutic agents have hugely increased. Advancements cover the entire spectrum of peptide R&D, from the development of peptide screening platforms, such as phage display and mRNA display, to the implementation of novel chemical strategies for more rapid and cost-effective synthesis of peptides with improved potency, selectivity, and pharmacokinetic properties, as well as the optimisation of formulations for peptide delivery.”
Betting Big on Peptides
Recent big investments into peptide-based platforms include Takeda’s setting aside of USD 3.5 billion in its partnership with Japanese peptide conjugate maker PeptiDream and Bayer’s research collaboration and license agreement with Danish biotech firm Gubra to develop peptide therapeutics to treat cardiorenal diseases, utilising Gubra’s peptide drug discovery platform to identify potential candidates. Back in 2017, Gubra also partnered with Boehringer Ingelheim to create peptide therapeutics to treat obesity.
CNS specialist Lundbeck has also been investing in peptides, with the recent acquisition of Alder Biopharmaceuticals. CEO Deborah Dunsire told PharmaBoardroom that this acquisition “brought a new focus on neuropeptides, which are involved in areas like migraine, cluster headaches, and other specialty pain syndromes.”
Neuropeptides … are involved in areas like migraine, cluster headaches, and other specialty pain syndromes
Deborah Dunsire, Lundbeck
She added, “Lundbeck has another neuropeptide-focused product that will enter Phase II trials later in 2021, indicated for specialty pain and potentially migraine. Both products are antibody or biologic products, a new capability for Lundbeck, which has a heritage in small molecules. Biologics have been used very successfully in many different categories of medicine, from rheumatoid arthritis to multiple sclerosis, and these drugs in migraine and specialty pain have a very specifically targeted effect using a biologic agent.”
Perhaps the most notable firm bringing peptide-based drugs to market today is fellow Danish firm Novo Nordisk, whose glucagon-like peptide (GLP-1) agonist Liraglutide is the current highest selling marketed diabetic drug worldwide. Novo is now increasingly prioritising the obesity space with another GLP-1 drug, Wegovy.
Not without Challenges
One biotech that has successfully navigated the peptide stability issue and in the process leapt ahead of its Big Pharma competitors, is Zealand Pharma, which recently gained its first FDA approval for Zegalogue, a rescue pen for severe hypoglycaemia in paediatric diabetes patients. CEO Emmanuel Dulac explains that “Zegalogue was made possible because of one major invention: liquid stable glucagon. Glucagon is a peptide – actually the most unstable peptide of all – and is notoriously difficult to put into a solution without losing the efficacy of the molecule within a few minutes. The challenge was finding or modifying a molecule which has the same efficacy as the natural glucagon but would be stable in solution.”
Much of the significant progress being made, and the effective drugs being developed, in metabolism and obesity are today coming through peptide-based innovation
Emmanuel Dulac, Zealand Pharma
Dulac continues, “Zealand started working on this many years ago, as did several other Big Pharma companies, but remarkably we were the first to reach the finish line, with others falling short in terms of toxicology, pharmacology, or pharmacodynamics.”
Expanding on the potential of peptides, Dulac adds that “Much of the significant progress being made, and the effective drugs being developed, in metabolism and obesity are today coming through peptide-based innovation.”
IRBM’s Toniatti cautions that the distinct characteristics of peptide therapeutics compared to other medicines need to be well understood by researchers. “Peptides are a distinct class of therapeutic agents with very unique properties,” he proclaims. “There are targets and therapeutic areas where they can outperform small molecules and antibodies. However, to develop a peptide therapeutic, it is of paramount importance to know exactly how to work with peptides and what can or cannot be achieved. Some notions and models which apply to small molecules and antibodies might not be valid for peptides.”
