Amylyx Pharma’s IPO lands $190M as ALS drug begins FDA review

 

Amylyx Pharmaceuticals has joined the public markets with a $190 million IPO that will support the company as it shepherds its amyotrophic lateral sclerosis drug through regulatory review, and if all goes well, a commercial launch as a new treatment for the neuromuscular disorder.

Cambridge, Massachusetts-based Amylyx boosted the size of the offering by 1.25 million shares. Initially planning to offer 8.75 million shares, Amylyx ended up offering 10 million shares at $19 apiece, which was the midpoint of the targeted $18 to $20 range. Those shares began trading on the Nasdaq Friday under the stock symbol “AMLX.” There was no pop for Amylyx’s stock price, which closed its first day of trading at $18.07.

Amylyx aims to treat ALS by addressing the death of neurons. The company’s drug, AMX0035, is comprised of two small molecules that each take a different approach to pathways associated with neuronal survival. The company contends that the two mechanisms combined offer the potential to help neurons live longer. In a placebo-controlled Phase 2 study, patients treated with the Amylyx drug showed improvement on measures of physical function in ALS patients. Based on those results, Amylyx submitted a new drug application to the FDA. Last week, the agency accepted that application under priority review and set a June 29 target date for a regulatory decision.

Before the FDA makes a decision, it will convene an independent panel of experts to discuss AMX0035’s safety and efficacy as well as any scientific questions regarding the drug. The date for that advisory committee meeting has not yet been set. In the meantime, a larger Phase 3 study is underway. The FDA went back and forth on whether the larger study was needed to support a drug application. Though the agency ultimately concluded that Amylyx could seek approval based on the Phase 2 data, the company is proceeding with the late-stage study to generate additional data on the drug’s safety and efficacy as it pursues regulatory approvals in other markets around the world.

According to the IPO filing, Amylyx traces its beginnings to a Brown University dorm room where, in 2013, co-founders Josh Cohen and Justin Klee set out to find an answer to the question of why neurons die. The duo’s research led to the development of AMX0035, the company’s only drug candidate so far. Though ALS is the drug’s first disease target, Amylyx notes that improving neuron survival has potential applications in many neurodegenerative disorders. A clinical trial is already underway testing AMX0035 in Alzheimer’s disease and tests in Wolfram disease are also planned.

Since its formation, Amylyx has raised about $234 million, most recently a $135 million Series C round of funding last July. Morningside Venture Investments is Amylyx’s largest stockholder, owning an 18.9% post-IPO stake, according to the prospectus. ALS Invest 1 owns 10.8%, while Viking Global Investors owns 8.8%.

As of the end of the third quarter of 2021, Amylyx reported a $125.7 million cash position. Combined with the IPO proceeds, the company plans to deploy about $100 million of its capital toward the regulatory review process of AMX0035 in ALS, as well as preparation for the potential launch of the drug—if it’s approved. Another $15 million is set aside to fund the ongoing Phase 3 clinical trial through to completion; $10 million is earmarked for expanding the company’s drug pipeline to other neurodegenerative disorders.

Two more biotechs joined the public markets in the first week of the new year. Here’s a look at the IPOs of CinCor Pharma and Vigil Neuroscience.

CinCor’s upsized IPO brings in $194M for hypertension drug trials

Patients who have high blood pressure can choose from a wide range of hypertension drugs, many of them older medicines and a few of them new. In many cases, these drugs aren’t enough to help patients control the condition. CinCor Pharma is developing a drug that offers a novel approach to hypertension and other cardiovascular and kidney conditions, and it has raised $193.6 million to finance clinical development of its most advanced program.

Late Thursday, Boston-based CinCor priced its IPO at $16 per share, which was the midpoint of the company’s projected price range. CinCor was able to boost the size of the deal, offering 12.1 million shares, up from the 11 million shares the company had planned. CinCor began trading on the Nasdaq on Friday under the stock symbol “CINC.”

Standard of care hypertension drugs include angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), both of which work by lowering levels of the blood pressure regulating hormone aldosterone. CinCor notes in its IPO filing that treatment with these drugs over a long period of time can lead to “aldosterone breakthrough,” in which levels of the hormone in the blood return to or exceed baseline levels. Mineralocorticoid receptor antagonists (MRAs) can lead to an increase in the synthesis of aldosterone, which then requires higher doses of the drug to compensate. MRAs also introduce multiple side effect risks.

CinCor’s lead drug candidate, CIN-107, is a small molecule designed to block the production of aldosterone by targeting the enzyme responsible for that hormone’s synthesis in the adrenal gland. The drug has reached Phase 2 testing in patients whose blood pressure is uncontrolled despite prior treatment with three antihypertension drugs. A separate Phase 2 study is was recently started in patients with uncontrolled hypertension despite treatment with one antihypertension agent. CinCor said in the filing it is also developing the drug for primary aldosteronism, a hormone disorder that occurs when too much of the hormone is produced. Another potential application of the drug is easing the complications associated with chronic kidney disease.

CinCor formed in 2018 as a subsidiary of CinRx Pharma, a Cincinnati-based biotech company whose business model is acquiring drug assets and advancing  them to the point of an exit, such as a licensing deal, a joint venture, or an IPO. In 2019, CinCor spun out as an independent company and licensed its lead drug from Roche. According to the prospectus, CinCor had raised $185 million prior to the IPO. Most of that cash was raised in October when the company closed a $143 million Series B funding round. The company’s largest shareholder is Sofinnova Investments, which owns a 14.8% post-IPO stake. Sofinnova Partners and 5AM Ventures each own 10.9%, while CinRx owns 8.1%.

At the end of the third quarter of 2021, the company reported a $141.7 million cash position. In its prospectus, CinCor said it planned to spend about $90 million to advance CIN-107 through the completion of Phase 2 testing in patients with uncontrolled high blood pressure. Another $37 million is budgeted for advancing that drug through a separate mid-stage test in primary aldosteronism. CinCor also plans to start a Phase 2 clinical trial enrolling chronic kidney disease patients who have uncontrolled blood pressure. That study is expected to begin in the first half of this year.

Vigil nabs $98M to test new approach to rare neuro disorder

Vigil Neuroscience, a company developing a treatment for a rare inherited neurological disorder that has no FDA-approved therapies, now has $98 million to test its experimental drug in humans. The biotech offered 7 million shares for $14 apiece, which was below the $15 to $17 price range that the company had planned. Those shares began trading on the Nasdaq on Friday under the stock symbol “VIGL.”

The disease target of Cambridge, Massachusetts-based Vigil is adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). The rare disease is a type of leukodystrophy, a disorder that leads to a wasting away of the white matter of the brain. The neurodegeneration of ALSP leads to changes in personality, cognition, and muscle function. The decline progresses to dementia and eventually, a vegetative state. According to Vigil, estimates place the affected U.S. population at 10,000 people.

ALSP stems from a mutation to the gene that produces colony stimulating factor 1 receptor, a protein expressed on the surface of microglia and macrophages, both of them immune cells found in the central nervous system. In the IPO filing, Vigil notes that colony stimulating factor 1 receptor shares a downstream signaling pathway with another protein, TREM2. Vigil aims to compensate for the loss of function in microglia by targeting TREM2.

Vigil’s drug, VGL101, is an antibody designed to activate TREM2. A Phase 1 test in healthy volunteers began last month. Vigil said in the IPO filing that it expects preliminary data will become available in the second half of this year.

Vigil formed in 2020, co-founded by venture capital firm Atlas Venture. The company licensed intellectual property for TREM2-targeting molecules from Amgen. In addition to the antibody approach taken by VGL101, the biotech is also developing a small molecule drug to target TREM2. According to the filing, Vigil had raised $120 million prior to the IPO, most recently a $90 million Series B round in August. Atlas is Vigil’s biggest shareholder, owning an 18.7% stake, according to the prospectus. Northpond Ventures and Vida Ventures own 13.6% and 11.8% respectively. Amgen’s stake is about 11.3%.

At the end of the third quarter of 2021, Vigil reported having $110.6 million in cash. Combined with the IPO proceeds, Vigil plans to spend about $105 million to advance the development VGL101 in ALSP and other rare leukoencephalopathies and leukodystrophies. Another $30 million is planned for research on small molecules that could treat neurodegenerative diseases associated with microglial dysfunction, while $20 million is set aside for additional R&D.

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