A diverse consortium, combining expertise from McGill University,
the Quebec government and private industry, has made significant
headway in the development of a novel new drug that could alleviate
insomnia and neuropathic pain. These advances were made possible
thanks to a $658,422 grant from the Quebec government (MEIE)
awarded by the Consortium Québécois sur la Découverte du Médicament
(CQDM), a $453,125 grant from Brain Canada and a combined grant
from Quebec-based Delmar Chemicals (now Minakem Montréal) and a
public institution (CIHR) amounting to a total of $1.6 million for
the research. (more information is available in the summary).
The journey began in 2007, with a scientific
discovery made at McGill and the Research Institute of the McGill
University Health Centre (RI-MUHC). Gabriella Gobbi, MD, PhD,
Professor, Department of Psychiatry at McGill University and
scientist at the RI-MUHC, was studying compounds that had the
potential to alleviate anxiety and depression. “One of these
compounds had an unexpected effect on a melatonin receptor in the
brain, sending the laboratory animals into a deep sleep,” she
recalls.
Melatonin is a hormone that helps regulate
circadian rhythms (our night and day cycle). It is released
primarily by the pineal gland at dusk in response to reduced light
levels, which is why it is sometimes called the ‘hormone of
darkness’. Melatonin naturally interacts with two receptors in the
brain, known as MT1 and MT2, which are selectively specialized in
controlling brain functions.
“By pure serendipity, the compound we tested
turned out to be an agonist for MT2,” explains Dr. Gobbi, who is
also a researcher at the RI-MUHC. The compound didn’t just induce
sleep, it also increased the restorative sleep, which is known as
non-rapid eye movement (NREM) sleep – the kind of deep sleep that
the body needs to stay healthy.
“Insomnia is a huge issue that can hinder daily
functioning and trigger major health concerns, such as depression,
diabetes and even cardiovascular disease,” says Dr. Gobbi.
According to estimates from the Canadian Institutes of Health
Research, nearly 24% of Canadians suffer from a sleep disorder.
Several years after this initial discovery, Dr.
Gobbi found that lower doses of the same compound reduced
neuropathic pain – a condition for which there are very few
treatments. “Most pain medication is dominated by opioids, which
have associated problems like addiction,” explains Dr. Gobbi. “The
identification of novel analgesics is of keen interest in medicine,
and we started to realize that the melatonin MT2 compound we had
been testing, might have great potential as a medicine to alleviate
pain and insomnia.”
Bringing a new drug to market is no small
achievement, however. Dr. Gobbi describes the journey as a daunting
Via Crucis. “Most drugs never make it to the clinical phase,” she
explains. “There’s a ‘Death Valley’ in drug development that is
notoriously hard to cross and requires significant resources,
frequently from venture capitalists, which are primarily profit
driven.” A recent study in the Journal of the American Medical
Association (JAMA) estimated the average cost of the investment
needed to bring a new medicine to market at $1.3 billion USD; other
estimates place the figure significantly higher.
CQDM, which facilitates collaboration between
universities, industry and government to accelerate scientific
discovery into vaccines, therapeutics and diagnostics, while
generating benefits for the Quebec economy, was able to help
identify a solution closer to home.
“We are incredibly lucky to be based here in
Quebec and have access to these resources,” explains Dr. Gobbi.
“Thanks to McGill’s leadership and administrative support, and
funding from the CQDM, Brain Canada and Delmar Chemicals, we’ve
been able to build a consortium that also includes members of the
pharmaceutical and biotech industry.”
The first challenge faced by the consortium was
to create a viable prodrug for toxicology testing, as the original
compound was insoluble because of its lipophilic properties. Enter
Robert Zamboni, PhD, Adjunct Professor of Pharmacology,
Biochemistry and Chemistry, whose team engineered a new drug from
the parent molecule that could be taken orally and metabolized in
the body. “It was a highly complex process that took over a year to
complete,” recalls Prof. Zamboni. There are many obstacles that
academic research needs to solve for translating an idea into an
approved drug to help millions of patients. Delmar Chemicals helped
McGill researchers to synthesize the drug in large scale and solve
biochemical issues. Industry partners, Delmar Chemicals and Evotec
were crucial collaborators in completing the synthesis of the drug
and the Pre-IND (Investigational New Drug) toxicology work on this
reengineered molecule. The GMP facilities and the R&D center of
Delmar Chemicals is still available to support the project in the
following steps until the final validation and approvals by Health
Authorities.
Dr. Gobbi and the team can now look ahead to the
first human trials. “It’s an incredible achievement that would not
be possible anywhere else,” she says. “I’m proud to be part of a
unique collaboration of organizations that have worked together to
harness Quebec intellectual property and develop a drug that has
the potential to positively impact the health of millions of
people.”
About the project:
In addition to the previously mentioned funding
partners, this project was made possible by the Canada Brain
Research Fund (CBRF), an innovative agreement between the
Government of Canada (through Health Canada) and Brain Canada
Foundation.
About Brain Canada:
Brain Canada plays a unique and invaluable role
as a national convenor of those who support and advance brain
research. A greater understanding of how the brain works
contributes to the prevention, diagnosis, treatment and cure of
disorders of the brain, ultimately improving the health outcomes of
people in Canada and around the world. To learn more, visit
Braincanada.ca @BrainCanada
About CQDM:
A biopharma innovation facilitatorCQDM is a
nonprofit biopharmaceutical research consortium whose mission is to
support and facilitate multi-party collaborative R&D aimed at
accelerating the translation or transformation of innovative
technologies into solutions addressing unmet medical needs, while
generating significant benefits for the economies of Quebec and
Canada. For more information, please visit: www.cqdm.org and follow
us on X/Twitter @CQDM_Canada and LinkedIn.
About Evotec SE:
Evotec is a life science company with a unique
business model that delivers on its mission to discover and develop
highly effective therapeutics and make them available to the
patients. The Company’s multimodality platform comprises a unique
combination of innovative technologies, data and science for the
discovery, development, and production of first-in-class and
best-in-class pharmaceutical products. Evotec provides high value
pipeline co-creating partnerships and solutions to all Top 20
Pharma and over 800 biotechnology companies, academic institutions,
as well as other healthcare stakeholders. Evotec has strategic
activities in a broad range of currently underserved therapeutic
areas, including e.g. neurology, oncology, as well as metabolic and
infectious diseases. Within these areas of expertise, Evotec aims
to create the world-leading co-owned pipeline for innovative
therapeutics and has to-date established a portfolio of more than
200 proprietary and co-owned R&D projects from early discovery
to clinical development. Evotec operates globally with more than
5,000 highly qualified people. The Company’s sites in Europe and
the USA offer highly synergistic technologies and services and
operate as complementary clusters of excellence. For additional
information please go to www.evotec.com and follow us on X/Twitter
@Evotec and LinkedIn.
About Minakem Montréal:
Minakem, a family-owned Belgian company with
$400M CAD revenues, recently acquired Delmar Chemicals Inc., the
largest Canadian, and only Quebec, facility producing APIs,
established in1941, and now known as Minakem Montréal. Minakem
Montréal has invested more than $80M CAD over the last 10 years in
OEB4 corticosteroids, controlled substances and other technologies.
It has been inspected by Canada Health, the FDA, KFDA and PMDA and
has strong regulatory support and R&D with a capacity of 174
M3, including 29 M3 for veterinary corticosteroids and controlled
substances. From kilo-lab to commercial up to OEB4, Minakem
Montréal recently launched new generics (USDMF) Apixaban,
Mirabegron, Solifenacin, Rosuvastatin, Lapatinib, Sorafenib,
Eslicarbazepine and Tofacitinib.
Media Contact:
Julia SerafinoCommunication and Marketing Coordinator
CQDM438-543-9498Jserafino@cqdm.org
Brielle Goulart Communications & Marketing Officer Brain
Canada 450-915-2253 Brielle.goulart@braincanada.ca
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