Beyond the secretome: targeting age-related immune decline

US biotech Immunis has developed an “immunomodulatory secretome” technology targeting age-related immune decline. With preclinical studies showing benefit in muscular atrophy, metabolic and vascular function, tissue inflammation, and immune cell function in a range of age-related disease indications, the Californian company is currently engaged in its first in-human clinical trial for muscle atrophy.

Longevity.Technology: The secretome refers to the substances that are secreted (released) by cells – exosomes, micro-vesicles, proteins, growth factors, hormones, cytokines, and other substances. The secretome is known to play a role in helping repair and regenerate our bodies, but these beneficial secreted factors decline with age. Immunis has developed a novel method to isolate secreted cellular factors that benefit immune system development, modulation, and health – and replenish them. To find out more about the company and its technology, we spoke to its Chairman, Dr Hans Keirstead.

Keirstead is a renowned stem cell expert and serial entrepreneur, founding and successfully exiting several biotech companies in the stem cell space. Back in the early days of the field, he became the first neuroscientist in the world to work with human stem cells.

“I didn’t realize at the time that my team was also the first in the world to derive high purity, adult populations from any type of stem cell,” he says. “To this day, everyone else in the world is getting 50 to 70% purity, and still today my group is the only one that’s getting high purity, 99.6% purity.”

Stem cell purity is key

This focus on stem cell purity has driven Keirstead throughout his career – he has a core team of scientists that have been working with him for more than 20 years.

Beyond the secretome: targeting age-related immune decline

“What we’ve done is to develop, in many different ways, this core technology of high purity differentiation of a multipotent stem cell into specific tissue-committed or cell-committed lineages,” he says. “And that’s really been the hallmark of my career.”

Building on the principle that, because stem cells can become any cell in the body, they have the capacity to treat any human disease, and Keirstead’s drug development path has taken him through treatments for spinal cord injury, ulcerative colitis, retinal disease, cancer, pathogens, and now aging. However, despite being a stem cell pioneer, he holds a dim view of many companies in the field – a perspective that he also extends to the longevity sector.

“To this day, nine out of ten stem cell companies are selling snake oil – they’re using stem cells as a marketing term,” he says. “And now, I find myself in the longevity field, where many companies’ claims are also absolutely ridiculous. And again, it’s a marketing angle.”

From cancer to longevity

So, what compelled Keirstead to lead a company in the “ridiculous” field of longevity? He cites his work on a stem cell-based cancer treatment at AIVITA Biomedical as a key driver.

“What’s important to realize in cancer is that every single cancer patient has a necessary precondition of immune deficiency,” says Keirstead. “And it doesn’t have to be a disease – lack of sleep, high stress, eating poorly and getting less exercise, are all major triggers that suppress the efficiency of your immune system. What happens with age is that your immune system starts attacking you and being very functionally inefficient, setting you up for cancer.”

This idea is relevant in longevity, says Keirstead, because the same thinking can be applied to aging.

“As you age, you birth your immune system less frequently and so it gets older and more tired with age, and it becomes dysregulated,” he says. “Every human experiences a decline in regulated immune function as they age – and virtually every manifestation of aging is due to a decline in regulated immune function. I’m not the only one to realize this, it’s just that modulating the immune system is very, very difficult.”

Secretome-powered immune modulation

Having become fascinated by addressing immune decline, Keirstead became convinced that the answer lay in developing a multi-active secretome product designed to modulate the immune system – the founding basis for Immunis.

“Immunis is an immunomodulator company, not an antiaging or longevity company, but an immune modulating one,” he stresses. “And we wanted to immunomodulate in a way that was prophylactic, so we developed a multicomponent secretome drug, with over 400 human proteins. We made it by manipulating stem cells into a cell type that secretes factors relevant to immune development and health. And that’s the first time in the world that has been done.”

Beyond the secretome: targeting age-related immune decline

For the next two years, Immunis provided its drug to leading professors across the aging field to test on animal models in their labs.  

“I’m not exaggerating, every one of them came back with positive results,” says Keirstead. “And, whether they were looking at arterial stiffness, or neuroinflammation, or muscle atrophy, or any other manifestation, they all noted that the treated animals just looked better.”

Targeting muscle atrophy

After preclinical studies of the secretome product showed it increased muscle mass, increased muscle strength, and diminished skeletal muscle fibrosis, Immunis is now treating patients in its first in-human clinical trial, looking at muscle atrophy in patients with knee osteoarthritis.

“We wanted to pick a manifestation of associated immune decline, and muscle atrophy is a strong fit,” says Keirstead. “100% of humans have muscle atrophy as they age, and it is absolutely proven to be immune modulated. There are all kinds of downstream effects, certainly tied to aging, for muscular atrophy. It triggers several other manifestations of aging: blood flow issues, nutrient supply issues, brain health, and so on.”

The Phase 1/2a trial is now moving into its second patient cohort and Keirstead says he expects the trial to conclude within six to 12 months, depending on recruitment rates. As far as potential future indications are concerned, Immunis is keeping its options open, but Keirstead says that metabolism, sports injury, and disease-related muscle atrophy are all on the table.

“But we are fully set and funded right now right through to Phase 3 for muscle atrophy in knee osteoarthritis,” he adds.

Interestingly, Keirstead reveals that Big Pharma is already showing an interest in goings-on at Immunis.

“We already have four major pharma companies looking at us, and I’m shocked by that,” he says. “This is the fifth company I’ve led, and I’ve never had Big Pharma interest so early. But they realize there is no drug for muscle atrophy, 100% of humans get it, and that can be said for multiple other manifestations of aging. Of course, everybody wants to be healthier. And I believe the best way to do that is immune modulation.”