Lilly Bets $630M on Pain Target Novartis Failed

Eli Lilly_Cristina Arias_Getty Images

Courtesy of Cristina Arias/Getty Images

Eli Lilly is expanding its pain management pipeline with a new asset from Belgium-based Confo Therapeutics. The two announced a licensing agreement for neuropathic pain candidate CFTX-1554 Thursday.

Under the terms of the agreement, Confo snagged $40 million upfront and will complete Phase I testing of CTFX-1554, which targets the angiotensin II type 2 receptor (AT2R). Lilly will take over from there. The company is in line for another $590 million if the asset proves its mettle.

Lilly also has the opportunity to develop other antibody candidates in Confo’s pipeline targeting the same receptor. Another $590M, including potential milestones, royalties and net sales, is on the line if Lilly moves forward with a second candidate, an antibody-based therapeutic. 

Confo’s platform stabilizes functional conformations of G-protein coupled receptors (GPCRs) – the body's largest and most diverse group of membrane receptors. While around 30% of drugs on the market target GPCRs, over half of these targets have proven notoriously hard to treat.

Cedric Ververken_Confo Therapeutics
Cedric Ververken

Cedric Ververken, CEO of Confo, told BioSpace that GPCRs are complicated because of their position in the lipid environment. These flexible proteins move around, making them tricky to target.

Confo uses ConfoBodies – single domain antibodies from llamas – which bind to the GPCR and stabilize the protein to enable more effective studies. 

Ververken said this “trick” could be utilized for small molecule and antibody discovery.

CTFX-1554 has the potential as a non-opioid treatment option for peripheral pain. Its target, AT2R, has already been proven effective by Spinifex Pharmaceuticals.

Novartis acquired the Australian company in 2015 for $200 million upfront. Spinifex’s AT2R antagonist showed a “consistent clinical improvement in pain intensity reduction” across two studies in two different pain populations, according to an NIH publication. Yet the program was quietly dropped mid-Phase II after toxicity to the liver was observed in long-term dosing in primates.

Based on Novartis’ learning experience, Ververken said Confo has high hopes for clinical efficacy.

“We have the same pharmacology on the target, but we don't have the issue with liver toxicity. Lilly was excited about our program because of that precedent molecule,” he said.

Chronic neuropathic pain is experienced in up to 17% of the population. These individuals have damage to the nerves outside of the brain and spinal cord due to diabetes, shingles, cancer and other conditions. Existing treatments are often ineffective and come with severe side effects like sedation or are in the form of opioids, which present a known danger of addiction.

CTFX-1554 has a peripheral mode of action, targeting the area of pain – arms or legs – but not the brain, avoiding these side effects.

Confo will invest the $40 million upfront payment into its other pipeline programs, currently marked as “rare disease 1 and 2.” The company hopes to nominate one for development by early 2024, Ververken said.

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