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Interview – Immodulon rises from the ashes of SR Pharma

Interview – Immodulon rises from the ashes of SR Pharma

Source EP Vantage
Company Immodulon TherapeuticsCelgeneSilence Therapeutics 
Tags Analysis, Free Content, Trial Results, Phase II, Vaccine, Oncology, Private Placement, Licensing, Interview
Date September 08, 2016

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 .”

Déjà vu

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,  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.

Caveat emptor

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 
Indication  Trial ID  Note 
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.