Praxis Precision Medicines Leads Way as Three More Biotechs Prep IPOs

Xconomy Boston — 

Praxis Precision Medicines kept mostly quiet about its research on central nervous system disorder (CNS) drugs until May, when it emerged from stealth and revealed $100 million in cumulative financing. Now the company is aiming to raise about that amount in an IPO that will fund clinical development of its drug pipeline.

Cambridge, MA-based Praxis is developing drugs intended to address the misfiring neuronal circuitry at the root of some neurological disorders. The company’s drugs are based on research into genetic mutations that regulate neuronal circuits in the brain whose dysregulation leads to the seizures in rare, inherited forms of epilepsy. But the company says in its IPO filing that additional research found that these genes also play roles in other neurologic and psychiatric disorders. Praxis is building on that research to develop drugs for a range of neurological conditions.

The most advanced Praxis drug candidate, PRAX-114, is a small molecule designed to target GABA, a neurotransmitter in the brain, as a way of treating major depressive disorder (MDD) and perimenopausal depression. While benzodiazepenes, a class of tranquilizing drugs, already target this neurotransmitter, these medicines come with side effects and aren’t currently approved for treating depression.

Praxis contends its tablet, a positive allosteric modulator of GABA that binds to a different site on GABA than benzodiazapenes, an approach that could offer a potent effect on depression and anxiety without the sedative effects associated with benzodiazepenes. The company points to another potential advantage compared to medicines currently in development for depression. For example, Sage Therapeutics (NASDAQ: SAGE) drug candidate zuranolone, which also targets GABA to treat MDD, has results in a published patent application that show its effect increased when taken after a meal, Praxis says in its filing. The company says it believes this food effect has led Sage to carry out clinical development with the requirement that the drug be taken with a high-fat meal.

“We believe that the ability to administer PRAX-114 with or without food is key for clinical and commercial success in MDD, as many patients struggle with adherence to medication and forcing a dietary regimen would impose further complications in this vulnerable population,” Praxis says in its filing.

In an ongoing Phase 2a study in Australia, Praxis says MDD patients treated with PRAX-114 showed “marked improvement” in depression scores within two weeks of treatment. The company plans to start a Phase 2/3 clinical trial in MDD in the fourth quarter of this year; preliminary results are expected in the second half of 2021. A Phase 2a study in perimenopausal depression is underway in Australia; preliminary data are expected in the second half of next year.

Another small molecule, PRAX-944, is in development for treating essential tremor. Praxis notes that the only FDA-approved essential tremor drug, the beta blocker propranolol, is poorly tolerated by patients. Another drug, the anti-convulsant primidone, is used off-label but can take six to eight weeks to find the right dose for maximum benefit. Furthermore, the drug brings sedative effects, balance problems, and an acceleration of osteoporosis with long-term use.

The Praxis essential tremor drug Praxis drug, which is currently in Phase 2a testing, is designed to block T-type calcium channels that research shows are a driver of the movement disorder. It’s the same target that Jazz Pharmaceuticals (NASDAQ: JAZZ) is aiming for with JZP-385, a drug that came via the acquisition of Cavion last year. That drug is currently in mid-stage testing. Praxis expects preliminary clinical data for its essential tremor drug will be ready in the first half of next year.

Praxis’s lead rare disease drug candidate, PRAX-562, is being developed for a range of rare CNS disorders, including pediatric epilepsy and adult cephalgia, a syndrome of cluster headaches. The drug is designed block sodium channels that modulate neurons, an approach also taken by other drugs. But Praxis says its drug is more selective, offering the potential for fewer side effects. The company expects to report Phase 1 data in the fourth quarter of this year.

Praxis was founded was founded in 2015 based on the epilepsy research of founders Kiran Reddy, David Goldstein, and Steven Petrou. According to the prospectus, the company has raised more than $282 million, most recently a $110 million Series C-1 financing in July. Blackstone is the company’s largest shareholder, with a 31.8 percent pre-IPO stake, according to the filing. Eventide Asset Management owns 12.9 percent; Vida Ventures owns 10.1 percent.

Praxis plans to use the IPO cash for Phase 2/3 clinical development of PRAX-114 in MDD, as well as mid-stage development of the drug in perimenopausal depression. The cash will also support Phase 2/3 testing of PRAX-944 in essential tremor. Additional funds will be spent on early-stage development of PRX-562. Praxis has applied for a Nasdaq listing under the stock symbol “PRAX.”

Two more biotechs joined the IPO queue. Here’s a look at their drugs and their clinical trial plans:

Aligos Therapeutics is developing a chronic hepatitis B antiviral therapy that could offer patients a functional cure—a reduction of the biological indicators of the virus below detectable levels. While currently available drugs called nucleoside analogs can suppress viral replication, Aligos says their functional cure rates are low and these drugs must be given long term. In its IPO filing, the South San Francisco-based biotech says it aims to overcome those limitations with multiple drugs that address different stages in the virus’s life cycle. By helping patients achieve a functional cure, the company hopes to help them avoid the risk of serious and potentially fatal liver problems such as cirrhosis and end-stage liver disease.

The most advanced Aligos drug candidate, ALG-010133, is an oligonucleotide designed to block a molecule called S-antigen transport oligonucleotide polymers (STOP). Aligos says its drug is similar to nucleic acid polymers (NAPs), a type of drug in Phase 2 development by Montreal-based Replicor. That intravenously administered drug is designed to block the release of subviral particles from liver cells. Aligos says its molecule is structurally similar to NAPs but has been “highly optimized” with chemical features intended to make it more potent and allow for subcutaneous dosing. A Phase 1 study of ALG-010133 is underway and is expected to be finished in the second half of 2022.

Other Aligos hepatitis B drugs in preclinical development include a small molecule, an antisense oligonucleotide, and a small-interfering RNA candidate. The company says it believes combinations of the therapies in its portfolio may lead to higher rates of functional cure. On Monday, Aligos announced that the FDA gave the company the green light to start a clinical trial testing its small molecule hepatitis B drug candidate, ALG-000184.

The fatty liver disease nonalcoholic steatohepatitis (NASH) is the second therapeutic area of focus for Aligos. NASH drug candidate ALG-055009 is a small molecule that targets thyroid hormone receptor-beta, one of several receptors for thyroid hormone. Compounds addressing the same target include VK2809, which Viking Therapeutics (NASDAQ: VKTX) is currently testing in a Phase 2b study, and Madrigal Pharmaceuticals (NASDAQ: MDGL) compound resmetirom, which has advanced to Phase 3 testing.

Aligos says tests suggest its drug may be more potent than the Viking drug and more selective than the Madrigal drug. The company says in its filing that its next steps are toxicology tests needed to advance to a clinical trial expected to start in the second half of next year. Aligos is also developing therapies for infections caused by coronaviruses, including SARS-CoV-2. That research is still in the discovery stage.

Aligos was founded in 2018. The company’s largest stockholders are Roche Venture Fund, Versant Ventures, and Baker Brothers, each owning a 12.1 percent stake. Aligos says in its filing that it has raised $186.9 million, most recently a $125 million Series B financing in January. As of June 30, Aligos reported a cash position of $88.1 million. Aligos set a preliminary $100 million target for its IPO. The company has applied for a Nasdaq listing under the stock symbol “ALGS.” The company says it will use the IPO proceeds for the manufacturing and clinical development of its hepatitis B and NASH drug candidates.

Tarsus Pharmaceuticals set an $86M goal as it eyes the completion of clinical testing and an expected regulatory submission for its lead drug, a treatment for Demodex blepharitis. Blepharitis is the inflammation and irritation of the eylid. Demodex blepharitis is caused by infestation by Demodex mites. Irvine, CA-based Tarsus says that according to published research, an estimated 20 million people in the US suffer from blepharitis. About 45 percent of those cases are caused by Demodex infestation.

Lead Tarsus drug candidate TP-03 is an eye drop containing lotilaner, which is part of a class of anti-parasitic molecules called isoxazolines, according to the filing. The drug is designed to block pathways in a mite’s central nervous system, leading to paralysis and eventual death. The company says its drug has low affinity to the same pathways in mammals, and therefore has no effect on the human nervous system.

Tarsus formed in 2016. According to the IPO filing, the company has financed its operations with $61 million in private placements. Its largest stockholder is Vivo Capital Fund, with a 21.4 percent stake, followed by Horowitz Group, a family office that owns about 12.9 percent. Tarsus is preparing for two Phase 3 studies, each enrolling about 350 patients. The first study, intended to further evaluate the safety and efficacy of TP-03, started earlier this month. Preliminary data are expected in 2021.

The second Phase 3 clinical trial, a confirmatory study, is expected to begin next year. The company expects the results from both late-stage studies will be enough to support a regulatory submission to the FDA. Tarsus says it also plans to seek regulatory approval in other markets, including Europe and Japan. If Tarsus completes its IPO, the company expects to trade on the Nasdaq under the stock symbol “TARS.”

Image: iStock/kasto80

 

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