Amgen vets launch Latigo Biotherapeutics to develop nonopioid pain relief

Latigo Biotherapeutics is launching after 4-plus years in stealth. The California biotech will develop pain drugs that could one day replace opioids.

Venture capital firm Westlake Village BioPartners, based just northwest of Los Angeles, debuted Latigo on Wednesday. Two Amgen veterans spearheaded Latigo’s growth: Westlake co–founding managing director Sean Harper, who was at Amgen for 16 years, culminating in leading R&D, and Westlake operating partner Desmond Padhi, who headed the pharma giant’s pharmacokinetics team and various other therapeutic divisions for 19 years.

Padhi is acting as interim CEO of Latigo, which already has $135 million in series A funding and a drug candidate in Phase 1 clinical trials.

Harper and Padhi set out with the specific intention of building a pain company in 2019. They looked for technology they could license, but with the exception of some chemistry from Baltimore’s Lieber Institute for Brain Development, they didn’t find much in the way of non-opioid pain relief—and nothing that was particularly far along in development, Harper says.

“We were going to have to build a de novo drug discovery capability here in LA if we’re going to do this right,” Harper says.

In neighboring Thousand Oaks, Amgen had made a strategic decision that would ultimately be a boon to Latigo. The pharmaceutical giant had just exited neuroscience, leaving 172 local employees without jobs. Harper contacted his old connections, and Latigo set up laboratory operations in Thousand Oaks, hired additional chemists, and secured investors.

The now-26-person team has developed a suite of nonopioid pain drugs. One, LTG-001, is in Phase 1 clinical trials, which are expected to end in time for the company to launch Phase 2 later this year. Another, LTG-4090, will enter Phase 1 trials this year if all goes according to plan, and more preclinical assets are in the pipeline behind it.

Both LTG-001 and LTG-4090 target a voltage-gated sodium channel called Na_v1.8. Na_v1.8 is primarily expressed in the peripheral nervous system, where it’s responsible for transmitting pain signals to the central nervous system—the brain and the spinal cord.

According to Padhi, the key is to ensure the compound gets to the peripheral nervous system without getting to the brain, where Na_v1.8 isn’t expressed. He says LTG-001 has been well tolerated and appears to have a good pharmacokinetic profile, according to data coming in from the Phase 1 trial. He declined to offer details as to when that data will be published.

“We’re trying to thread the needle, to stay out of the brain but get these compounds into the nerve,” Harper adds.

Na_v 1.8 is a genetically validated target, meaning that mutations in the gene that codes for it are known to cause problems, like abnormal neuronal firing in nerve and cardiac disorders. It is also a clinically validated one. Vertex Pharmaceuticals’ pain drug candidate, VX-548, works by blocking the same channel, and it recently met all its primary end points in a Phase 3 study for acute pain and a Phase 2 study for chronic pain.

What remains to be seen is whether these sodium-channel blockers can outperform the drugs they’re trying to replace: opioids. Vertex’s compound couldn’t beat Vicodin—hydrocodone and acetaminophen—which was used as a comparator in the Phase 3 study.

But Latigo’s leaders aren’t concerned about that. On the contrary, they say VX-548 provides a blueprint for LTG-001 and LTG-4090 to succeed or to even best the larger pharma’s drug candidate. And the new class of drugs doesn’t come with the same harmful side effects of opioids, most prominently addiction.

“[LTG-001] has all the properties we believe could make it a best-in-class molecule,” Padhi says. “It has a high degree of selectivity for Na_v1.8 versus other Na_vs and other receptors. It has no central nervous system exposure.”

Latigo’s next step is to hire a full-time CEO. Board chair Nancy Stagliano, CEO of a neurological and immune disorder start-up called Neuron23, is leading that charge. She says she’s looking for someone with experience heading up both private and public companies. Asked if that means Latigo is looking to take advantage of the warming initial public offering market, she says, “Nothing is off the table.”

“We’re looking at a lot of different options,” Stagliano says. “I think there are a lot of opportunities for Latigo.”