Promethera buys TNF drug to boost cell therapy NASH strategy

Promethera CEO John Tchelingerian (Promethera)

Promethera Biosciences has stepped up its NASH plans with the takeover of Baliopharm. The buyout gives Promethera control of a TNF receptor 1 inhibitor it hopes will amplify the effects of cell therapy HepaStem.

Mont-Saint-Guibert, Belgium-based Promethera moved into NASH research a couple of years ago in the belief its liver progenitor cells can help people with the disease. The acquisition of Baliopharm for an undisclosed fee is intended to complement that ongoing cell therapy effort by setting Promethera up to combine HepaStem with an anti-TNF antibody.

“It will add an additional layer and amplification of our anti-inflammatory, anti-fibrotic approach with HepaStem,” Promethera CEO John Tchelingerian, Ph.D., said.

Promethera’s interest in the antibody stems from data suggesting it antagonizes TNF receptor 1 but leaves TNF receptor 2 free to function normally. Receptor 1 is overexpressed in NASH on hepatic cells involved in collagen production and fibrosis, making it a target of interest for Promethera. But the importance of TNF receptor 2 for liver regeneration means high specificity is critical.

Promethera thinks Baliopharm’s asset has such specificity, although an early version of the drug gave the latter company pause when it entered phase 1 five years ago. Baliopharm saw agonistic effects at very low doses, prompting it to go back to the lab and develop a monovalent agent that bound to TNF receptor 1 without causing a clustering effect.

That done, Baliopharm has landed a takeout. Promethera will now test the drug in combination with HepaStem in animal models with a view to creating a regimen that better addresses the complexity of NASH than either drug can in isolation.

Promethera is still a long way from clinically validating either drug, though, let alone the combination. The biotech was already well behind NASH frontrunners Genfit and Intercept when it made the disease part of its R&D strategy in 2016. Since then, Promethera has fallen further behind. Promethera had planned to get into the clinic in the second half of 2017 but its position toward the back of the pack led it to rethink its strategy.

“The competitive landscape was very crowded in the initial segment of NASH, translating from NAFLD to NASH F1, F2 and rarely to F3,” Tchelingerian said, referring to the F0 to F4 scale used to stage fibrosis.

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Seeing that more advanced programs were likely to sew up those stages of the disease, Promethera began testing HepaSem in a wider range of models. The resulting data led Promethera to position its cell therapy as a treatment for F4 and decompensated F4, the most advanced stages of the disease. Patients classed as F4 have cirrhosis. Decompensated F4 patients have symptoms related to cirrhosis, such as jaundice.

Gilead is enrolling compensated F4 patients in phase 2 and 3 trials of selonsertib and some of the NASH drugs it is combining with the ASK1 inhibitor. But it is excluding decompensated patients from the studies and many other NASH programs are focused on people with F1 or F2 fibrosis. That leaves a gap for a drug designed to treat the sickest NASH patients.

Promethera wants to fill that gap and has brought new investors on board to support its plans. Reflecting the cell therapy specialist’s ongoing appeal to Japanese strategic and financial investors, Promethera has pulled in €9.3 million ($11.4 million) from Shibuya, Shinsei and some existing backers.

The sum is relatively small for a biotech that raised €20 million-plus series B and C rounds. But the latest financing is an hors d'oeuvre, not the main event. Promethera is preparing a bigger round for later in the year.