Orphazyme, a Danish late-stage biotech developing protein therapies for rare neurodegenerative diseases, filed on Friday with the SEC to raise up to $115 million in an initial public offering. The company is currently listed on the Nasdaq Copenhagen under the symbol “ORPHA.”
Orphazyme is developing heat shock proteins to develop novel therapies for neurodegenerative orphan diseases. The company submitted an NDA for product candidate arimoclomol with the FDA for Niemann-Pick disease Type C (NPC) in July 2020, and it plans to submit a marketing authorization application to the EMA in the 2H20. In its Phase 2/3 trial of arimoclomol in NPC, the company observed evidence of slowing of disease progression.
The Copenhagen, Denmark-based company was founded in 2009 and plans to list on the Nasdaq under the symbol ORPH. Orphazyme filed confidentially on June 30, 2020. BofA Securities, Cowen and Guggenheim Securities are the joint bookrunners on the deal. No pricing terms were disclosed.
Relevant Profile: ORPH
Friday, September 4, 2020
Danish rare disease biotech Orphazyme files for a $115 million US IPO
Precision oncology biotech PMV Pharmaceuticals files for $100M IPO
PMV Pharmaceuticals, an early stage biotech developing targeted therapies for cancer, filed on Friday with the SEC to raise up to $100 million in an initial public offering.
The company’s lead candidate, PC14586, is designed to potently and selectively correct p53 misfolding caused by a specific p53 mutation while sparing wild-type p53. The company is initially pursuing a tumor-agnostic development strategy and submitted an IND for PC14586 in August 2020, with a Phase 1/2 trial planned for the 2H20.
The Cranbury, NJ-based company was founded in 2013 and plans to list on the Nasdaq under the symbol PMVP. PMV Pharmaceuticals filed confidentially on June 26, 2020. Goldman Sachs, BofA Securities, Cowen and Evercore ISI are the joint bookrunners on the deal. No pricing terms were disclosed.
Relevant Profile: PMVP
Oncology biotech Prelude Therapeutics files for a $100 million IPO
Prelude Therapeutics, a Phase 1 biotech developing small molecule therapies for cancer, filed on Friday with the SEC to raise up to $100 million in an initial public offering.
The company’s first clinical candidate, PRT543, is currently in a Phase 1 trial in select solid tumors and myeloid malignancies in patients who are refractory to or intolerant of established therapies. Interim Phase 1 results indicate dose-dependent increases in exposure and target engagement, and the company has observed early signs of clinical activity. The company expects clinical data in the 1H21.
The Wilmington, DE-based company was founded in 2016 and plans to list on the Nasdaq under the symbol PRLD. Prelude Therapeutics filed confidentially on July 23, 2020. Morgan Stanley, Goldman Sachs and BofA Securities are the joint bookrunners on the deal. No pricing terms were disclosed.
Relevant Profile: PRLD
CM Life Sciences closes $442.8M IPO
CM Life Sciences (CMLF) closed its initial public offering of 44.3M units at $10/unit; includes 5.78M units issued post underwriters exercising option in full.
Units listed on Nasdaq, commenced trading on September 2.
Each unit consists of one share of Class A common stock and one-third of one redeemable warrant; each whole warrant exercisable to purchase one share of Class A common stock at $11.50/share.
The company is formed for the purpose of effecting a business combination.
Intends to focus its search for business combination targets in life sciences industry segments, often fragmented, – life sciences tools, synthetic biology and diagnostics.
https://seekingalpha.com/news/3611830-cm-life-sciences-closes-442_8m-ipo
Trial: Oral Surgery Helps in Sleep Apnea
In a randomized trial, surgery to widen and stabilize the soft palate and reduce tongue size improved outcomes among patients with moderate-to-severe obstructive sleep apnea (OSA) for whom conventional treatments had failed.
In early findings from the multicenter trial, palatal surgery combined with minimally invasive tongue volume reduction reduced the number of sleep apnea events and improved patient-reported sleepiness at 6 months, compared with ongoing medical management, according to Stuart MacKay, MD, of the Illawarra ENT Head and Neck Clinic in Wollongong, Australia, and colleagues.
As shown in the team’s study online in JAMA, other polysomnography measures of sleep apnea severity, including arterial oxygen saturation and cortical arousal frequency, as well as partner-reported snoring and patient-reported quality of life were also improved in the surgery patients at 6 months, but 57% of patients still had moderate to severe residual sleep apnea on polysomnography at 6 months, and oxygen saturation continued to fall below 85% in some patients.
The Sleep Apnea Multilevel Surgery (SAMS) study is among the first to explore a combined palatal and tongue reduction surgical approach, and the investigators noted that additional research will be needed to understand the clinical utility, long-term efficacy, and safety of the surgical strategy for treating OSA.
“Most patients with OSA have multilevel obstruction, including tongue size due to fat deposition. Thus, this trial of multilevel surgery supports a broader role for upper airway surgery to manage OSA and expands on an earlier randomized clinical trial of multilevel minimally invasive surgery in patients with mild disease,” the researchers wrote.
In addition, they said, this multilevel approach showed a greater treatment effect than has been shown in trials of uvulopalatopharyngoplasty alone, with a similar adverse event risk.
Writing in an accompanying editorial, Sean M. Caples, DO, and colleagues from the Mayo Clinic in Rochester, Minnesota, said the study “should be considered a platform for the new era in clinical trials of upper airway surgery for OSA.”
In an interview, Caples praised the rigorous design of the study, which was conducted at six surgical sites across Australia, but called the findings “somewhat disappointing.”
“After surgery there was still a large group of patients with residual sleep apnea, so I suspect that this approach is probably not going to be the game changer everyone is looking for in the treatment of sleep apnea,” he told MedPage Today.
In addition, while continuous positive airway pressure is highly effective for improving OSA symptoms, a large number of patients either won’t use or cannot tolerate it, he added. https://tpc.googlesyndication.com/safeframe/1-0-37/html/container.html
Study Details
The SAMS trial included 102 adults with symptomatic moderate or severe OSA for whom conventional treatments had failed. Patients were enrolled from August 2014 to November 2017, with follow-up until August 2018.
Study participants were randomized to have either multilevel surgery (51 patients) or ongoing medical management (also 51), which included advice on OSA-related lifestyle and health interventions such as sleep positioning, weight loss, and management of nasal obstruction.
Surgery consisted of modified uvulopalatopharyngoplasty to widen and stabilize the velopharynx and seven to nine submucosal insertions of a radiofrequency-in-saline wand to reduce tongue volume. The seven surgeons recruited to perform the multilevel procedure attended a training workshop designed to standardize the surgical technique.
The primary study outcomes were the apnea-hypopnea index (AHI: the number of apnea and hypopnea events per hour, with more than 30 indicating severe OSA) and the Epworth Sleepiness Scale (ESS: range of 0 to 24, with more than 10 indicating pathological sleepiness). The researchers assessed baseline-adjusted differences between the two treatment groups at 6 months.
Mean participant age was 44.6 (SD 12.8); 18% were women, and 89% completed the trial.
The mean AHI was 47.9 at baseline and 20.8 at 6 months among the surgery group and 45.3 at baseline and 34.5 at 6 months among the medical management group (mean baseline-adjusted between-group difference at 6 months, −17.6 events/hr, 95% CI −26.8 to −8.4, P<0.001).
The mean ESS was 12.4 at baseline and 5.3 at 6 months in the surgery group and 11.1 at baseline and 10.5 at 6 months in the medical management group (mean baseline-adjusted between-group difference at 6 months −6.7, 95% CI −8.2 to −5.2, P<0.001).
Two participants (4%) in the surgery group had serious adverse events, including one patient who had a myocardial infarction on postoperative day 5 and one who was hospitalized for observation following hematemesis of old blood.
In their editorial, Caples and colleagues said the study represents “a solid foundation for future investigations, although several issues deserve consideration.”
“First, surgery was effective at preventing upper airway collapse in some patients but not in others, suggesting that selection criteria will need to be refined in future trials,” the editorialists continued. “Second, as in other treatment trials of OSA, women and minority populations were underrepresented, highlighting the importance of including patients from these groups in future trials. Third, because the follow-up time was only 6 months, longer-term data from this trial and future trials will be needed to test the durability of treatment effect over time. It is conceivable that with aging or weight gain, the surgical effect on soft tissue recedes.”
Caples and co-authors concluded that comparative efficacy trials are needed to compare outcomes from the multilevel surgical strategy with other surgical procedures, including maxillomandibular advancement and upper airway stimulation.
Disclosures
Funding for the study was provided by the National Health and Medical Research Council of Australia, Flinders University, the Repat Foundation, and others.
MacKay reported receiving grants from the National Health and Medical Research Council of Australia, Flinders University, and The Repat Foundation 2013 Prabha Seshadri Research Grant during the conduct of the study and nonfinancial support from Genio-Nyxoah, and grants from Garnett-Passe Rodney Williams Foundation and Illawarra Health and Medical Research Institute outside of the study; co-authors also reported receiving financial compensation unrelated to the research.
Caples reported no disclosures; co-editorialists reported grants from the ResMed Foundation and the Paul and Ruby Tsai and Family Fund Career Development Award at Mayo Clinic outside the study; and royalties from UpToDate for chapters on management of obstructive sleep apnea.
Primary Source
JAMA
Secondary Source
JAMA
Source Reference: Mansukhani MP, et al “Upper airway surgery for obstructive sleep apnea” JAMA 2020; DOI: 10.1001/jama.2020.9332.
https://www.medpagetoday.com/pulmonology/sleepdisorders/88473
Pfizer, BioNTech ‘quietly’ usher a 5th COVID-19 jab into the clinic
BioNTech and partner Pfizer have been working on four vaccine candidates against COVID-19, snagging FDA fast-track tags for two of them and pushing one into a 30,000-patient phase 3 study. Now, the duo is adding a fifth shot on goal, slated to enter a phase 1/2 study this month.
“Company management confirmed to us this fifth BNT162 COVID-19 construct to enter the clinic uses modified mRNA (modRNA) like BNT 162b2, which is currently in Phase 2/3 registrantion enabling trial,” wrote SVB Leerink analyst Daina Graybosch, Ph.D., in an investor note Friday.
“They said this new candidate showed preclinical promise and could be a follow-on candidate,” Graybosch wrote, adding that Pfizer, meanwhile, has picked a different candidate, BNT162c2, as another potential follow-on.
All five efforts fall under the partners’ BNT162 program, but they use different mRNA formats and target antigens. Like its latest addition, dubbed BNT162b3, the two fast-tracked candidates use a nucleoside-modified RNA, or modRNA, while another prospect uses a uridine-containing mRNA, or uRNA, and the fourth uses self-amplifying mRNA.
Pfizer and BioNTech started the phase 2/3 study of its most advanced candidate, BNT162b2, in late July, with the goal of testing the vaccine in up to 30,000 people aged 18 to 85. The trial is expected to involve about 120 sites around the world, with a focus on those with a high prevalence of COVID-19 still in the community.
The trial will assess whether the vaccine can prevent COVID-19 infection in people who have never been infected by SARS-CoV-2, as well as those who have. The partners expect to report interim data in October and, “assuming clinical success,” they are “on track” for a regulatory filing the same month, they said when they kicked off the study.
If the jab snags approval or authorization, the plan is to supply up to 100 million doses by the end of 2020 and about 1.3 billion doses by the end of 2021.
The duo may have trailed Moderna, which was first to get an mRNA vaccine—or any vaccine—for COVID-19 into the clinic, but its multicandidate approach could put it in a better spot than its rival.
“We like BioNTech’s drive to iterate in innovation and believe multiple shots-on-goal puts them in a good position for the long-term catch-up vaccination, re-vaccination, and/or pandemic stockpiling markets,” Graybosch wrote.
German lawmakers urge shorter coronavirus quarantine
Politicians have backed recommendations by top virologist Christian Drosten for quarantine in suspected COVID-19 cluster cases to be reduced to five days. They hope the measure would then find greater social acceptance.
Lawmakers from across Germany’s political spectrum are calling for a reduction in the quarantine period for suspected coronavirus cases to just five days.
The self-isolation time for people at risk of COVID-19 infection through cluster contact is currently 14 days.
Calls for a rethink come after leading virologist Christian Drosten — who has been credited with much of Germany’s success in tracking and tracing the virus — recommended a shorter period. He said evidence suggested the virus would not be infectious five days after symptoms became apparent.
Emerging scientific evidence has made a rethink on the rules necessary, according to Karl Lauterbach, health spokesman for Germany’s Social Democrats (SPD) — the junior coalition partner to Chancellor Angela Merkel’s conservatives.
“If we limit the quarantine time to five days, social acceptance for the measure would be significantly higher,” Lauterbach told German daily Die Welt.
“We know that the vast majority of people are no longer contagious five days after the start of symptoms, even if the PCR test is still showing a positive result,” said Lauterbach, who is also a professor of health economics and epidemiology at the University of Cologne. The presence of the virus does not necessarily mean the patient is infectious.
Lauterbach added that such a change could initially appear difficult to justify. “But, if scientific knowledge makes a change in the measures seem sensible, you have to do it,” he said.
Christine Aschenberg-Dugnus, health spokeswoman for the pro-business Free Democrats, agreed that the change would encourage greater public acceptance and deny ground to coronavirus conspiracy theorists.
“For the broad mass of the population, it could be sensible to initially go into a shortened quarantine when there is a suspicion that there has been contact with an infected person, and to conclude this with a negative test,” she said.
Detlev Spangenberg, health spokesman for the far-right Alternative for Germany (AfD), said Drosten’s comments supported his party’s position that the existing measures were “hasty and not applied in a balanced way.”
The health policy spokeswoman for Merkel’s conservatives, Karin Maag, said a study was currently underway by both Germany’s health ministry and the Robert Koch Institute, the country’s public health agency.
The aim, she said, was to “evaluate the existing situation on quarantine and then, in communication with European partners, to submit a report.” The result could lead to a shortening of quarantine, Maag added.
In a podcast by German broadcaster NDR, virologist Drosten on Tuesday repeated an earlier recommendation that the quarantine period might be shortened.
Drosten said such a reduction was at the “pain threshold” of what was acceptable in disease control terms, but that it might garner more public support for coronavirus measures.
He said the patients could be tested after five days to see not only if they were positive for the virus, but also if they were infectious.
German Health Minister Jens Spahn is holding a video conference with his counterparts from EU states Friday. The ministers will discuss the potetnial for a Europe-wide ruling on quarantine.
https://www.dw.com/en/coronavirus-quarantine-germany/a-54811004