A MATTER OF BALANCE

Galenisys Newsletter : September 2026

Table of Contents

• TALES FROM FARAWAY PHARMA: “Boiling Australia”
  By Steve Biddulph

• IT'S BEEN A RED, RED, SUMMER
  What else could describe the last few months?
  By Tony Dunford

• GLP-1 medicines: Reshaping the pharmaceutical industry
  By Richard van Duyse

• “EAT, TRAVEL, WORK, SLEEP, EVERYBODY” - Not too much, not too little.
  Orexins are the next big thing
  By Tony Dunford

TALES FROM FARAWAY PHARMA: “Boiling Australia”

by Steve Biddulph

Fellow of Royal Society of Biology. Board level pharma experience. QSM and Aseptic Manufacturing & Control Expertise. Galenisys Managing Director.

“Boiling Australia”

Our site in Melbourne had undergone a recent routine GMP inspection by the Therapeutic Goods Administration (The “TGA” - equivalent of the FDA). Following the inspection, the TGA refused to renew the GMP certificate for the site, to our surprise.

The reason for this, was that the TGA were not satisfied with the quality of the water used to manufacture Oral Liquids. They wanted the site to agree to boiling all water before use in manufacture.

We looked through the water system and found that the water produced was actually highly purified water with Reverse Osmosis, with EDI and UV treatment before storage and distribution. The distribution system was under continuous ozone injection, which additive was properly controlled, monitored, and destroyed before points of use.

Water samples produced no detectable contamination from points of use.
Checks on the challenges to the oral liquid preservative systems showed that the preservative systems were robust and proven when challenged by Pharmacopeial organisms and a range of local isolates.

Given our confidence the site director set up a meeting with the TGA in Canberra which I was invited to participate in. “How long a drive is it?”, I asked. “Far too long” was his reply. People just don’t understand how big Australia really is when glancing at a map of the continent. Sydney to Canberra measures about an inch.

So we flew to Canberra and met with the TGA head of inspections and the resident microbiologist, in their HQ.
We produced all of the drawings and data on the water system and the challenges to the oral product preservative systems. After our presentation the TGA microbiologist raised the issue of “What if” there was an isolate in the water system at some point in the future and that we had not challenged the preservative systems with it. In response we detailed the challenges and showed him the data on a whole range of organisms, bacteria and fungi, which comprised the challenges.

“Have you tested the systems against the gram-negative bacteria recently isolated from oil shale in Western Australia?”, he asked. Obviously, we had not done this and despite pointing out that there was no risk of these organisms ever getting into our purified water.

We reiterated our scientific rationale, results, and description of our modern industry compliant process. But to no available; sadly, encountering a bureaucratic organism immune to scientific logic.

As a result, our necessary renewal of the GMP Certificate was achieved by a process change to “Boil, Baby, Boil”.

Steve Biddulph

IT'S BEEN A RED, RED, SUMMER

What else could describe the last few months?

By Tony Dunford

The red of widespread wildfires. Red showing the heat wave areas. Trump’s red card trade. Red lines crossed by Infantino. Holiday delays: tourists “see red”. A summer “Red in tooth and claw”.

And that's on top of our usual doses of red: Red - don't enter. Red - it's closed. Red - stop at the lights. Red: “don't walk”. Yes, red has a lot of negative connotations.

So, it's nice to hear something nice about red!!

Because there are surprising benefits of RED LIGHT!! potentially including better skin, faster wound healing, and reduced vision loss.

0ozing mouth ulcers are a possible side effect of radiation and chemotherapy treatments for cancer. The ulcers make it hard for patients to eat worsening their suffering. Some must be fed by tube. However light emitting diodes “LEDs” tuned to the red end of the spectrum and placed into a patient's mouth improve ulcer woes in more than half of cases.

Red, and infrared, light treatments are known as Photobiomodulation or “PBM” therapies, (the former used for some time to treat age-related decline in eyes and skin respectively).

Now PBM is also showing promise in the treatment of traumatic brain injuries Alzheimer's and Parkinson's diseases and even some psychiatric disorders.

The long wavelengths of red and infrared light penetrate tissue better than others in the spectrum. This light reaches & is absorbed by molecules of the protein cytochrome c oxidase (“CcO”) which helping provide the energy for the ATP molecule which powers much of a cell's biochemistry. The red light reactivates CcO molecules that have been switched off by nitric oxide a “reactive oxygen species (“ROS”). More active CcO molecules means more fuel for cellular repair etc. And a cell gets more antioxidant enzymes that neutralise a wide range of other damaging ROS molecules.

As people age more ROS molecules are produced accidentally, reducing their ATP production. But PBM allows you to adjust the ageing mechanism claims Glenn Jeffrey a neuroscientist at UCL. In a pilot study attempting a proof of concept applied to the retina, results found that volunteers > 40 years old saw their colour contrast vision improve by an average of 20%. More R&D will be needed before clinical treatments are available.

In 2024 another published study reported that non-diabetic people exposed to red light had blood glucose peaks 7.5% lower than in the control group, after both had a sugary drink. The finding might point a way forward for regulating blood sugar levels.

At the University of Birmingham David Davison, a neurosurgeon & colleagues are developing a (patented) device made of red-light LEDs embedded in silicon & planned as a test implant in pigs.

Eventually patients with brain and spinal cord injuries could benefit by redlight slowing surging cell deaths that happens within days of the accident, which can lead to life in a wheel chair. Experiments on cell structures and rodents saw reductions in cell deaths of 20% or more.

Brain damaging Parkinson's and Alzheimer's diseases are both linked to ROS oxidative stress. Early-stage PBM research suggests it could help those who don't respond to standard medications. Red light has been found to aid postoperative recovery reducing pain and expediting healing, & in physiotherapy PBM decreases inflammation and boosts blood circulation.

Professor Jeffrey explains that whereas humans evolved in sunlight nowadays eg windows tend to block infrared. & office lighting is by blue tinging LEDs.
The “Wellness” industry has jumped on this early knowledge, to sell the benefits of eg red light masks and blankets, infrared saunas,, skin rejuvenators & sleep enhancers etc; but the extent of their benefits is unproven, in the absence of peer reviewed, large scale, dosage-controlled studies including control groups.

Meanwhile for self-medication, your daily stroll, jog, or outside activities, several times a day will get you your red-light doses.

Tony Dunford

GLP-1 medicines: Reshaping the pharmaceutical industry

By Richard van Duyse

Experienced international vaccine industry consultant. Specialized in project & operational management, facility design, start-ups, & technology transfers. Bachelor of Applied Science (B.Sc.).

The impact, & implications of the new weight loss therapy on the pharmaceutical industry is huge. It is not merely a matter of a successful new class of medication, but of medications that influence the strategy of the entire healthcare sector.

1. One of the largest growth markets ever
Weight loss medication has transformed the treatment of obesity from a relatively small market the fastest-growing pharmaceutical segment. This is because obesity is a chronic condition that affects hundreds of millions of people worldwide, a number that is increasing rapidly.

For pharmaceutical companies, this vast expanding market of patients on the long-term medication justifies investments of billions of euros in research, production, and distribution.

2. From diabetes to obesity
These weight loss products were originally developed for diabetes. Since then, obesity has become potentially far larger market for many companies.

The acknowledged side effects of the original products, reduced muscle mass during weight loss; “modest” weight loss, weight gain increasing medication etc; and the inconvenience of, or aversion to injections; have refocused R&D. Targets are new obesity medications; combination therapies; side effect reductions and oral forms.

3. Huge market size has spurred intense competition
Large pharma companies are investing heavily in products with improved efficacy, fewer side effects, & more convenience, in addition to lowering production costs & increasing production capacity.

In contrast many smaller biotech companies are focusing on specific development candidates which may enable them to partner with (or be acquired by) the major players with established Sales & Marketing networks and deep pockets.

4. New economic models
For the pharmaceutical industry, a key difference is that obesity is increasingly viewed as a chronic disease rather than a lifestyle problem.

The vast long-term revenue for pharma companies, is a large unwelcome long-term cost for Health Insurers, & National Health Systems. There will be intense negotiations on reimbursement between these parties; as well as close collaboration with research institutions, clinicians & doctors.

And as we detailed in last month’s article on of Eli Lilly’s “reinvention”, new distribution channels are emerging for these preventive medicines to be “direct to the consumer”.

5. Investments in production
The demand for weight loss therapy medication has become so great that companies are investing billions in new factories; the production of injection pens & supply of active ingredients; together with expansion of global distribution.
Production capacity has even become a strategic competitive advantage.

6. Change in research priorities
Weight loss medicines have shown that a single drug can influence multiple diseases.

As a result, extensive research is being conducted into applications for cardiovascular diseases; kidney diseases; fatty liver disease; sleep apnea; addictions; neurodegenerative disorders, such as Alzheimer's disease (still experimental).

This allows the same medication to be approved for multiple indications.

7. Impact inside & outside the pharmaceutical sector
The huge revenue streams for some means large turnover losses for others.

Sectors such as bariatric surgery; dietary products; food products; fitness outfits; medical devices; & health insurance will need to readjust to major changes in demand.

8. Challenges for the industry
Despite the opportunities, there are also challenges for pharma companies:

• high development and production costs;
• pivotal discussions regarding affordability and reimbursement;
• pressure from governments to keep prices under control;
• costs of monitoring long-term safety and effectiveness;
• competition threats as more similar products enter the market.

Conclusions
Weight loss therapy has fundamentally changed the pharmaceutical industry.
Whereas obesity was formerly a relatively limited therapeutic area, it has now become one of the most important growth markets.

For pharmaceutical companies, this means not only major commercial opportunities but also a shift in research, production, and long-term strategy.
At the same time, this development raises questions regarding accessibility,& affordability.

Richard van Duyse

“EAT, TRAVEL, WORK, SLEEP, EVERYBODY” - Not too much, not too little.

Orexins are the next big thing

Tony Dunford

There's a French expression to describe the daily grind: “Metro, boulot, dodo” (travel, work, sleep), to which could be added “bouffe” - food. Everybody needs food and sleep. Hunger and sleep are “master systems” that keep the body in balance. When the systems are unbalanced illness follows.
GLP-1 based drugs have proved so useful for moderating food intake, and orexins could do the same for sleep.

Drugs based on glucagon-like peptide 1 (GLP- 1) a hormone released by the gut after a meal, have recently transformed medicine. They began as treatments for diabetes before proving successful in helping people slim. (They have since shown benefits in the fields of heart disease kidney disease sleep apnea and other ailments).

Drug makers are now betting that a neuropeptide, orexin (or “hypocretin”), could be a similar blockbuster. Existing in 2 forms: orexin-A and orexin-B, it regulates arousal, wakefulness, & appetite. The pair are neurotransmitters, chemicals that carry messages between neurons. And a new generation of drugs designed to mimic their effects is approaching the market.

Earlier this month the FDA approved oveporexton made by Takeda, as the first orexin agonist (which stimulates the same cell surface receptors), for narcolepsy sufferers. Alchermes and Irish biotech is developing a competitor. As we reported last month Eli Lilly bought Centessa, a biotech with an orexin drug** in early trials, to further benefit from the peptide boom. Morgan Stanley estimates the market for narcolepsy and related sleep disorders could reach $16 bn pa in 2035.

As Orexins help coordinate sleep, attention motivation, and the brain's reward system, drugs could eventually treat depression, ADHD, & addiction.
Orexins once released, & depending on their function, lock onto either receptor OX1R or OX2R switching them on. OX2R activation stimulates several wakefulness promoting systems and keeps them working together “rather like the conductor of an orchestra”. OX1R is more involved with reward and motivation.

Orexin antagonists promote natural sleep
Orexin antagonists turn the OX2R “conductor” off & so promote sleep. They treat insomnia better with less risk of dependence and fewer long-term problems than conventional sleeping pills which induce sedation rather than natural sleep and often lose effectiveness over time.

(Of course, an excellent way to sleep well is to have Galenisys working on your quality problems).

Now if other drugs could correct otherwise faulty orexin signalling in narcolepsy type 1NT1 sufferers, they could perhaps treat many other sleep disorders. Turning orexins back on has proved harder than switching them off, but Takeda's persistence resulted in the oveporexton approval.

Such orexin agonists should produce more natural and stable wakefulness with fewer side effects and less potential for abuse than stimulants used in existing treatments which manage symptoms rather than the disease itself. These can improve alertness but may also cause anxiety, elevated blood pressure, and poor sleep. Some also carry a risk of addiction.

Lilly's orexin agonist** is being tested against 3 types of narcolepsy & early data are encouraging.
Other companies are studying orexin agonists for the treatment of ADHD, and the common sleep disorder apnoea.

The reward and motivation role of other orexin receptor OX1R could be exploited in products for curbing addiction but much more research is needed before there are marketable drugs. (Another early hope is that boosting the orexins signal in the brain could help treat depression and even enhance motivation).
Tony Dunford

Footnote: The insomnia medication suvorexant (Belsomra), was approved in 2014 by the FDA, as were orexin antagonists lemborexant (Dayvigo)[82] and daridorexant (Quviviq). Daridorexant was EMA approved in 2022 for sleep initiation and maintenance disorders.

THE QUOTE:
“Men are not made to be crowded together in anthills ……………….
the more they crowd together the more they corrupt each other” Rousseau

THE GOOD NEWS
Is the discovery of Manikomycin a new antibiotic whose novel action on bacteria resistant to other antibiotics was reported in “Nature” by the researchers at McMaster University in Ontario Canada. Produced by the soil bacterium streptomyces rimosus (as is oxytetracycline) it was isolated by advanced fractionation. The researchers are advancing the antibiotic to clinical testing after finding it non-toxic to human cells.