Biotechs never die, they just get reincarnated with a new name and a slightly different focus. This is probably too simplistic a view of Immodulon, the private UK group that emerged from obscurity this week, but the debt it owes to SR Pharma is significant none the less.
SR crashed when its mycobacterium-based lead, SRL172, flunked a major lung cancer study back in 2001. Undeterred, Immodulon is pursuing the same theme, and armed with phase II data and backed by one of SR’s founders it is taking an unorthodox route to raising funds for pivotal studies.
“We have a big philanthropic bent in the company – we’d love to become another Wellcome, that’s the plan. That’s why we’re sticking to philanthropic money,” Immodulon’s chairman, Dr Charles Akle, tells EP Vantage. He has raised £35m ($47m), mainly from private, high-net-worth individuals, and now wants to raise another £35m.
Rejection of the typical venture capital funding structure makes Immodulon unusual, as does targeting cancer with an inactivated bacterium. But then Immodulon is not your typical biotech.
And Dr Akle has a new bargaining chip: data from Image-1, a phase II pancreatic cancer trial of Immodulon’s lead, IMM-101, have just been published in the British Journal of Cancer. The main purpose of the trial – safety – was demonstrated, but it is an efficacy hint that particularly excites Dr Akle.
More than a hint?
“It’s more than a hint," he states. "If the primary endpoint had been based on metastatic disease alone we’d be home and dry.”
Pancreatic cancer, a graveyard for biopharma development, is at least capable of giving a survival result quickly, and in all-comers median overall survival was 6.7 months for IMM-101 plus gemcitabine versus 5.6 months for gemcitabine alone.
This was not statistically significant, and moreover the hazard ratio's upper bound exceeded 1.0. But in metastatic patients, a prespecified subgroup, the 2.6-month benefit hit p=0.01.
IMM-101 is a naturally occurring, heat-killed bacterium, Mycobacterium obuense, which Dr Akle says acts as an immune system modulator: “Firstly it induces in the immune system a tuning effect; it also acts as an immunoadjuvant ... functioning heavily on both innate and adaptive immunity.”
He also makes much of its effect on multiple pathways, in contrast to single-target strategies, which cancers usually end up evading. “Think of the London Underground,” he argues. “If you knock out Oxford Circus you’ll cause chaos for a week, but very quickly people will go around [it].”
It is true that the importance of bacteria in oncology is only now starting to be appreciated – witness the interest generated by studies of the gut microbiome. But does it not all sound a little unscientific?
Dr Akle reckons enough is known for regulators to be satisfied. “We know which pattern recognition receptors we trigger in the initial immune response ... we know about a trigger on gamma-delta T cells, we know about triggers that turn T cells into cytotoxic T lymphocytes.”
Seasoned UK biotech watchers who remember SR Pharma might at this point feel a sense of déjà vu; SR had tried and failed with the same approach, its lead, SRL172 flunking studies first in tuberculosis and then in lung cancer.
SRL172 was based on a closely related bacterium, M vaccae, and here too Dr Akle sees a silver lining: “Nobody understood at the time the difference between a vaccine and an immunomodulator. If you look at patients [in the lung cancer trial] who had five or more doses they actually did far better; the results were astounding.”
After SRL172 failed SR switched focus to RNAi and was renamed Silence Therapeutics. One of its founders, Dr John Stanford, founded Immodulon together with Dr Akle, focusing on IMM-101 – a separate mycobacterial idea of Dr Stanford's. Initial money was donated by one of Dr Akle’s patients.
Immodulon also now owns SRL172, and is developing it as IMM-201 for tuberculosis prevention in Aids patients in sub-Saharan Africa – on a philanthropic basis, of course.
Yet despite the optimism there are caveats about the Image-1 data, most obviously the fact that its design predated two now established first-line options, Folfirinox and Abraxane.
It is possible therefore that IMM-101 numerically beating gemcitabine does not reflect the real world. Dr Akle disagrees, pointing to Folfirinox and Abraxane toxicity, as well as the fact that Abraxane is unavailable or not reimbursed in many jurisdictions.
Another problem is that after IMM-101 treatment some patients in Image-1 went on to receive Abraxane. While this would not have affected the one-year statistical analysis it could have helped one patient survive three years.
Phase III will aim to recruit 350 metastatic patients in Europe and the US, similarly adding IMM-101 on top of gemcitabine. Combinations could be a future aim, since "gemcitabine plus IMM-101 is very good, but we can improve on it dramatically”.
First the money has to come in, neither from a venture capitalist – “the valuation would be intolerable” – nor flotation; “We’re not at IPO, nor do we particularly want to go for IPO,” says Dr Akle.
How about a pharma licensing deal? “Absolutely. We’ll sup with the devil, even if we have to use a long spoon.”
|Selected IMM-101 studies|
|Pancreatic cancer||Image-1, NCT01303172||110 pts, IMM-101 on top of gemcitabine. 2.6mth OS benefit in metastatic subgroup.|
|Melanoma||NCT01308762||18 end-stage pts. Possible publication at SITC conference in Nov 2016.|
|Melanoma||NCT01559818||Named-pt, long-term extension; 6/18 pts alive after 6 years.|
|Colorectal cancer||NCT01539824||18-pts, short study aiming to demonstrate antigen release.|