NeuroRx says a planned $500-million merger with Big Rock Partners Acquisition Corp. will help fuel its pipeline treatments—including a COVID-19 therapeutic that the company hopes to launch in 2021.

NeuroRx, a small molecule drug developer, has announced plans to combine with publicly-traded Big Rock in a deal expected to close in the first half of 2021. The combined company is expected to trade on Nasdaq under the symbol NRXP.

Based in Radnor, PA, NeuroRx is partnering with Geneva-based Relief Therapeutics to develop aviptadil—recently renamed Zyesami™ and once called RLF-100™—as a countermeasure for COVID-19. Zyesami is under study in two placebo-controlled ongoing Phase IIb/III trials: The AVICOVID-2 study evaluating inhaled Zyesami in patients with moderate and severe COVID-19 (NCT04360096) and the COVID-AIV study assessing intravenous Zyesami in patients with critical COVID-19 with respiratory failure (NCT04311697).

Jonathan C. Javitt, MD, MPH, NeuroRx’s Founder, Chairman and CEO

Earlier this month, NeuroRx and Relief said they met the 165 patient enrollment target agreed with the FDA for the COVID-AIV trial, for which NeuroRx and Relief are set to announce topline data in early 2021. NeuroRx plans to bring Zyesami to market later in 2021: “We hope to be launching a life-saving drug,” Jonathan C. Javitt, MD, MPH, NeuroRx’s Founder, Chairman and CEO, told GEN Edge.

Zyesami is also under study in an FDA-sanctioned Expanded Access Protocol (EAP; NCT04453839) assessing patients with severe comorbidities (such as organ transplant, recent heart attack, and cancer) that rendered them ineligible for COVID-AIV. In October, NeuroRx and Relief said 81% of the 21 ICU patients with critical COVID-19 and respiratory failure, who were treated with Zyesami in a 45-patient open-label study conducted under the EAP, survived beyond 60 days, compared to 17% of 24 control patients.

“Four of five aviptadil-treated patients initially on Extracorporeal Membrane Oxygenation (ECMO) have been decannulated, compared to 3 of 13 ECMO-treated controls,” Jihad G. Youssef, MD, of Houston Methodist Research Institute, and colleagues stated in a report posted in August on the preprint server SSRN.

Since July 2020, more than 300 patients with critical COVID-19 and respiratory failure have been treated with Zyesami in the company’s randomized and expanded access studies.

VIP treatment

Zyesami is a synthetic formulation of human Vasoactive Intestinal Peptide (VIP), a 28 amino-acid natural peptide known to reduce inflammation in the lungs by inhibiting cytokines and protecting the alveolar type II cells that are believed to be an entry route for SARS-CoV-2 to invade the lungs. VIP, which is concentrated in the lungs, is believed to inhibit coronavirus replication, prevent cell death, and upregulate the production of surfactant.

“It’s like a perfectly designed guided missile against the coronavirus,” Javitt said. “It binds only to the alveolar type 2 cell; it doesn’t bind to the rest of the lung. And in that cell, it blocks coronavirus replication. It increases surfactant production, and it blocks cytokines from being formed in a block cell death.”

“If you talk to any molecular drug developer and say, ‘Okay, I want you to build a drug that does these four things,’ they’ll look at you like you’re crazy. And yet, this 28 amino acid peptide that’s been around for 65 million years does all of those things, and probably more things that we haven’t figured out yet,” Javitt added.

The drug originally showed promise in treating acute respiratory distress syndrome (ARDS) from sepsis, and may even have a role in COPD. “The COVID opportunity came along because we have an investor in common with Relief Therapeutics, which proposed it to us. But I think there are a number of very exciting directions for aviptadil,” Javitt said.

Research on VIP stretches back some 50 years. Studies showing the VIP to prevent lung injury in patients by protecting type II epithelial cells were published by the late Sami I. Said, MD, of what is now Renaissance School of Medicine at Stony Brook (NY) University and the Veterans Administration Medical Center in Northport, NY.

Said was Distinguished Professor at Renaissance, and former Chief of the Pulmonary and Critical Care Division and Associate Chief of Staff for Research at the VA. A half-century ago, Said’s research focused on identifying a hormone that caused blood pressure to drop in patients who developed a pulmonary embolism. He took a sabbatical at Sweden’s Karolinska Institutet, where he partnered with Viktor Mutt, PhD, to discover VIP, then published several papers on VIP, for which Stony Brook was awarded an FDA Orphan Drug Designation in 2001.

“He couldn’t buy enough lung [material] to do his research. So he bought tons of [animal] intestine from the local slaughterhouses, and isolated this hormone he was looking for from the intestinal tissue,” Javitt recalled.

Company outlook

Javitt is expected to remain at the helm once its merger with Big Rock is completed, as are three other NeuroRx executives: Chief Commercial Officer Robert Besthof; Chief Financial Officer William Fricker; and Corporate Secretary Alessandra Daigneault, JD.

NeuroRx’s other lead drug, NRX-100/101, is a sequential two-drug regimen being developed for bipolar depression, with a Phase IIb/III clinical study launched in 2017.

The regimen consists of NRX-100 (ketamine), an anesthetic approved for surgical procedures but not so far for psychiatric indications; and NRX-101, an oral fixed-dose combination of two FDA-approved drugs: D-cycloserine, an NMDA receptor modulator; and Lurasidone (Latuda®), a 5-HT2a receptor antagonist. NRX-101 has advanced to Phase III with the FDA’s Breakthrough Therapy Designation, a Special Protocol Agreement, Biomarker Letter of Support, and Fast Track Designation.

The regimen is based on a patented discovery by Javitt that drugs targeting both the NMDA and 5-HT2A receptors in the brain could treat both depression and suicidality without the hallucinations caused by most NMDA inhibitors and without the potential for suicide attributable to other 5-HT2A inhibitor drugs. Unlike ketamine and its derivatives, NRX-101’s two component drugs are not classified as controlled substances by the Drug Enforcement Administration (DEA). NeuroRx reasons that as a result, NRX-101 could be given at home after an initial stabilization with NRX-100 in a clinical setting.

Under the merger, Big Rock has agreed to issue to NeuroRx’s current equity holders 50 million shares of Big Rock common stock representing $500 million of equity consideration, assuming a value of $10 per common share. Another 25 million shares of Big Rock common stock will be issued to NeuroRx pre-merger equity holders if, before the end of 2022, RLF-100 receives emergency use authorization by the FDA, and if the FDA accepts the Company’s filing of its application to approve RLF-100.

$100M “Earn-out”

NeuroRx pre-merger equity holders could also receive a $100 million cash “earn-out” if, before December 31, 2022, either the FDA approves Zyesami and it is listed in the FDA’s “Orange Book”—or if the FDA approves NRX 100/101 and it is listed in the FDA’s “Orange Book.”

The boards of both NeuroRx and Big Rock have unanimously approved the proposed merger, which is also subject to approval by stockholders of both companies, as well as other customary closing conditions.

Javitt, who also co-chairs NeuroRx’s Scientific Advisory Board, will be one of seven members of the board being formed by the combined company. All officers and members of Big Rock’s board will resign once the merger is completed.

Based in Delray Beach, FL, Big Rock is a publicly-traded “blank check” company formed for the purpose of entering into a merger, stock exchange, asset acquisition, stock purchase, recapitalization, reorganization, or other similar business combination with one or more businesses or entities.

“We at NeuroRx are excited to be combining with Big Rock Partners and its base of dedicated investors,” Javitt said. “Our focus from the outset has been to serve patients with life-threatening conditions who are not served by traditional pharmaceutical approaches. As we have gotten to know our new partners at Big Rock Partners, it is clear to us that they share the same values and commitment to putting the patient first.”