The discussion on Covid-19 antiviral drugs focused on Recently authorized Pfizer and Merck drugs, Now provides patients with oral alternatives to injection or infusion therapy. Other companies are also looking for more convenient oral formulations, including Pardes Biosciences, which now has $274 million to support the clinical development of pills with the same viral targets as Pfizer but with potential dosage advantages.
Just before the Christmas holiday, the shareholders of FS Development Corp. II approved The special purpose acquisition company merges with Pardes in Carlsbad, CaliforniaTo lay the foundation for the newly merged company Start trading It is listed on NASDAQ this week under the ticker symbol “PRDS”. The SPAC merger came less than two years after the company was established at the beginning of the Covid-19 pandemic. Since then, the biotech company has advanced the development of the main antiviral drug candidate PBI-0451, which is currently being tested in humans.
Pardes drugs belong to a class of drugs called protease inhibitors. Proteases are enzymes that break down proteins. They are like a pair of scissors, cutting a long protein chain and allowing different enzymes in the chain to play a role in the virus replication process. By binding to proteases, protease inhibitors prevent them from cleaving, thereby preventing this critical step in the viral replication process.
The concept of blocking viruses by targeting proteases is an ancient concept. The first protease inhibitor to enter the market was an HIV drug approved in the mid-1990s. Such drugs are also approved for the treatment of hepatitis B and C. PBI-0452 is designed to target the main protease or Mpro. If this protease sounds familiar, it may be because it is aimed at the same goal as the newly authorized Pfizer antiviral drug Paxlovid.Pfizer Phase 2/3 Test Results Report Compared with placebo, taking the drug within three days of the onset of symptoms reduced the risk of hospitalization or death by 89%. When given within five days, the risk was reduced by 88%.
The protease inhibitor in Pfizer’s medicines is called Nimarivir. It must be used in combination with another drug, ritonavir. This drug is usually combined with HIV drugs to help them work better. In the treatment of Covid-19, ritonavir slows the breakdown of Paxlovid, helping it stay longer in the body and maintain a higher concentration. But getting this benefit means that patients need to take an extra ritonavir tablet for every two tablets of Paxlovid taken. During the five-day treatment course, the patient needs to take a total of 30 pills.
Pardes uses its protease inhibitors as a way to target Mpro without the need for additional enhancers. The effectiveness of this method still needs to be confirmed in clinical trials, but if it is effective, it may mean that patients do not need to take so many pills. However, Pardes did not specify how many pills a dose of PBI-0452 consists of.
Pardes was founded by Uri Lopatin, a biotech industry veteran whose experience includes holding executive positions at Gilead Sciences, Roche, and Assembly Pharmaceuticals. Lopatin told MedCity News in an interview in September that biotechnology was formed to respond directly to the pandemic.
“I am an infectious disease doctor, and when a new pandemic virus begins to spread, one of the reactions is that we will need a new oral antiviral drug and vaccine — a variety of [products],” Lopatin said. “Unfortunately, this prediction is correct. “
Lopatin added that Pardes is based on the science of HIV protease inhibitors, which can be traced back decades. Almost since people have known about the coronavirus, Mpro has stood out as a promising protease target. When the virus enters the cell, the RNA from the virus is translated into protein chains called polypeptides. The chain was cut 11 times by Mpro. Lopatin said that Mpro’s role in cutting means that it is important to viruses and therefore a valuable drug target. Other features also make Mpro a good target. On the one hand, it starts working early in the virus replication cycle.
“The more upstream you can break the pathogen life cycle, the more attractive the goal becomes,” Lopatine said. “The virus has fewer opportunities to do bad things.”
In addition, Mpro is a conservative protease-even if the virus mutates, it will not change much-so it is likely to continue to be an effective target for new variants. Every known coronavirus requires this protease, Pardes said, which expands the potential of its drugs to tackle coronavirus infections other than Covid-19. In preclinical studies, the company stated that its drugs have shown activity against a series of coronaviruses including SARS-CoV-2. In addition, Mpro is not found in humans, so targeting it is unlikely to cause adverse effects.
The characteristics of Mpro make it an attractive target for Pfizer and Pardes, and it has also aroused the research interest of other companies. Exscientia is working with the Bill and Melinda Gates Foundation to develop Mpro targeted small molecules; Others include Cortexyme and Arbutus Biopharma. So far, these research work is in the pre-clinical development stage.
The first phase of the PBI-0452 test is a dose escalation study designed to recruit approximately 120 healthy adult volunteers. Registration starts in August.According to November Investor introductionSo far, the Pardes drug has been well tolerated, and no known studies have been discontinued. The trial researchers reported that the adverse reactions were mild. Pardes expects to obtain preliminary Phase 1 data in the first quarter of 2022. The company said that these results will determine the dosage for the next phase of clinical testing, which may begin in mid-2022. This phase 2/3 test will recruit patients with mild to moderate Covid-19.
Pardes’ cash income from the SPAC merger was broken down into $199 million in the trust account of FS Development Corp. II, plus funds and accounts advised by Foreste Capital, RA Capital Management, Frazier Life Sciences, and T. Rowe Price Associates US$75 million in private investment by GMF Capital, EcoR1 Capital, Monashee Investment and Gilead Sciences. The funds will be used to continue PBI-0451’s Phase 1 trial, initiate Phase 2/3 studies, and produce drugs for clinical trials. Pardes also plans to further develop its product line, including applying its technology to viral targets other than coronavirus and non-virological applications.
Photo by Paders Biosciences
