Sigilon Therapeutics on deck for IPO

• Sigilon Therapeutics (SGTX) has filed a prospectus for a $100M IPO.
• The Cambridge, MA-based biotech develops cell therapies based on its Shielded Living Therapeutics (SLTx) platform that combines advanced cell engineering with innovations in biocompatible materials.
• Lead candidate is SIG-001, designed to prevent bleeding episodes in people with moderate-to-severe hemophilia A by continuously secreting factor VIII. An 18-subject Phase 1/2 trial commenced last month.
• 2020 Financials (9 mo.): Collaboration revenue: $9.6M (-13.5%); Operating Expenses: $48.2M (+19.3%); Net Loss: ($39.3M) (-34.9%); Cash Consumption: ($44.5M) (-21.6%).
• https://seekingalpha.com/news/3636298-sigilon-therapeutics-on-deck-for-ipo
  

Icahn reduces Herbalife stake, increases IEP stake: 13F

• Carl Icahn reduces his Herbalife stake (NYSE:HLF) to 20.5M shares from 35.2M previously.
• Boosts stake in Icahn Enterprises (NASDAQ:IEP) to ~213.6M shares from 205.1M shares.
• https://seekingalpha.com/news/3636345-icahn-reduces-herbalife-stake-increases-iep-stake-13f
  

Glaxo's linerixibat misses endpoint in liver disease study but some positives

• GlaxoSmithKline (GSK +1.2%) announces mixed results from a Phase 2 clinical trial, GLIMMER, evaluating linerixibat for the treatment of cholestatic pruritis (severe internal itching believed to be caused by excess circulating bile acids) in patients with primary biliary cholangitis (PBG), a chronic liver disease characterized by the progressive destruction of the bile ducts. The data were presented at The Liver Meeting.
• 147 participants received once-daily 20 mg, 90 mg or 180 mg or 40 mg or 90 mg twice-daily of linerixibat or placebo for 12 weeks. The primary endpoint was the mean change from baseline in a scale called Mean Worst Daily Itch Score.
• The main objective was not achieved in the overall population but three treatment groups (40 mg & 90 mg twice-daily and 180 mg once-daily) showed statistically significant improvements in itch compared to control.
• There was also a statistically significant relative reduction in itch in a subgroup of patients with moderate-to-severe pruritis in the 40 mg twice-daily arm.
• On the safety front, the most common treatment-related adverse events were diarrhea and abdominal pain. The safety profile was considered acceptable to proceed to Phase 3 studies.
• https://seekingalpha.com/news/3636239-glaxos-linerixibat-misses-endpoint-in-liver-disease-study-positives-seen
  

FDA OKs Merck's Keytruda for triple-negative breast cancer

• The FDA approves Merck's (NYSE:MRK) Keytruda (pembrolizumab), combined with chemo, for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1.
• The indication is the 26th in the U.S. for the PD-1 inhibitor.
• https://seekingalpha.com/news/3636313-fda-oks-mercks-keytruda-for-triple-negative-breast-cancer
  

Pfizer/BioNTech up after hours on Trump comments on COVID-19 availability

• Pfizer (NYSE:PFE) and development partner BioNTech SE (NASDAQ:BNTX) are both up 1% after hours in apparent reaction to comments from President Trump that emergency use authorization (EUA) of their vaccine, currently dubbed BNT162b2, will be coming soon and the vaccine will be broadly available as soon as April.
• This past Monday, the companies announced that the vaccine was 90% effective in preventing SARS-CoV-2 infection. Pfizer may file an EUA application as soon as month-end.
• Moderna (NASDAQ:MRNA), close behind with mRNA-1273, is up 1% as well as is AstraZeneca (NASDAQ:AZN).
• https://seekingalpha.com/news/3636329-pfizer-biontech-perk-up-1-after-hours-on-trump-comments-on-covidminus-19-availability
  

Inhaled Interferon May Aid Hospitalized COVID-19 Patients

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Hospitalized COVID-19 patients receiving SNG001, inhaled nebulized interferon beta-1a, were more likely to show clinical improvement than those receiving placebo, a small pilot study in the U.K. found.

Patients randomized to receive SNG001 for 14 days had greater odds of improvement on the World Health Organization (WHO) ordinal scale for clinical improvement (OSCI; OR 2.32, 95% CI 1.07-5.04, P=0.033) on day 15 or 16 compared with those receiving placebo, reported Tom Wilkinson, PhD, of University of Southampton in England, and colleagues.

Moreover, patients in the intervention group were more likely to revert to an OSCI score of 1, or no limitation of activities, on day 15 or 16 (HR 2.19, 95% CI 1.03-4.69, P=0.043), the authors wrote in the Lancet Respiratory Medicine.

Type 1 interferon is "one of the first cytokines induced by viral infection of a cell and is a primary driver of innate immune responses in the human lung," the researchers noted. They explained that SNG001 is a formulation of recombinant interferon beta "for inhaled delivery by [nebulizer]," which has been well tolerated in clinical studies among patients with asthma or chronic obstructive pulmonary disease.

Interestingly, an accompanying editorial by Nathan Peiffer-Smadja, MD, and Yazdan Yazdanpanah, MD, PhD, both of Assistance-Publique Hôpitaux de Paris in France, noted that interferon failed in preliminary results from the WHO's SOLIDARITY trial.

In addition to different composition of the two trials, the editorialists found another key difference: route of administration. SOLIDARITY used subcutaneous interferon beta-1a, whereas this trial used nebulized therapy that "delivers interferon beta-1a directly to the respiratory tract."

"[Nebulized] therapy allows targeted delivery of interferon to the lungs, where it can induce the expression of interferon-stimulated genes that participate directly ... or indirectly ... in the antiviral response in the mucosa," Peiffer-Smadja and Yazdanpanah wrote.

For the new study, Wilkinson and colleagues randomized adults hospitalized with COVID-19 symptoms, who tested positive for SARS-CoV-2 via reverse-transcriptase polymerase chain reaction or point-of-care test to receive either SNG001 or inhaled placebo for 14 days. Primary outcome was change in clinical condition on the WHO OSCI (a 9-point scale where 0 means no infection and 8 means death).

From March 30 to May 30, a total of 48 patients were randomized to SNG001 and 50 to placebo in an intent-to-treat analysis. Patients were a mean age of 57, 59% were men, and 80% were white. Baseline comorbidities included hypertension, cardiovascular disease, diabetes, chronic lung condition, and cancer.

Demographic characteristics between groups were similar, although the SNG001 group had more severe disease, with 77% of patients receiving oxygen therapy vs 58% in the placebo group. Mean duration of symptoms before treatment initiation was 10 days.

In the SNG001 group, the odds of improvement were more than three-fold greater on day 28 versus placebo (OR 3.15, 95% CI 1.39-7.14, P=0.046), the authors noted.

Five patients underwent intubation or died compared with three in the intervention group. Over the 14 days of treatment, patients in the intervention group were more than twice as likely to recover.

There was no difference in the odds of hospital discharge or time to hospital discharge between groups. By day 14, 73% of the placebo group and 69% of the intervention group had been discharged.

Regarding safety, 54% of patients in the intervention group and 60% in the placebo group reported treatment-emergent adverse events, the most common of which was headache (15% and 10%, respectively). Fewer patients in the intervention group had serious adverse events compared with placebo (15% vs 28%), and the most common were respiratory failure (6% vs 12%) and pneumonia (6% each).

One patient in the placebo group had multiple organ dysfunction syndrome and one had pulmonary embolism, which caused them to withdraw from the study. These patients later died, along with a third patient in the placebo group, who died of COVID-19 pneumonia.

In their editorial, Peiffer-Smadja and Yazdanpanah noted that the study was not powered to assess mortality outcomes, and called for large randomized trials to investigate the effectiveness of nebulized interferon beta-1a, speculating that it might benefit patients in an early stage of disease in the outpatient setting.

"In patients with severe COVID-19, an exacerbated inflammatory response has been identified as a cause of pulmonary complications, and interferon beta-1a -- a pro-inflammatory cytokine -- could increase the inflammatory response and be associated with safety issues," the editorialists wrote.

They added that safety will also be a concern, as "[nebulization] of interferon has no marketing [authorization] for any indication yet."

Notably, COVID-19 guidelines from the National Institutes of Health recommend against the use of interferon, except within a randomized clinical trial.

Disclosures

The study was funded by Synairgen Research, U.K., a University of Southampton spin-out company.

Wilkinson disclosed support from the NIHR Southampton Biomedical Research Centre, my mhealth, GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, and Synairgen Research. Several co-authors are employees of Synairgen Research, including one who is a director of Synairgen (the parent company of Synairgen Research). Several co-authors also disclosed a patent on inhaled interferon-beta in SARS-CoV-2 patients and patents related to antiviral therapy for respiratory diseases, specifically interferon-beta. In addition, one co-author is managing partner of TranScrip Partners, and other co-authors disclosed support from Synairgen Research, TranScrip Partners, Boehringer Ingelheim, Celgene, BioMerieux and BioFire, Roche, Janssen, Cidara Therapeutics, Randox, Qiagen, Novartis, AstraZeneca, Teva, and NIHR Oxford Biomedical Research Centre.

Peiffer-Smadja and Yazdanpanah reported having no competing interests.

Primary Source

Lancet Respiratory Medicine

Source Reference: Monk PD, et al "Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: A randomised, double-blind, placebo-controlled, phase 2 trial" Lancet Respir Med 2020; DOI: 10.1016/S2213-2600(20)30511-7.

Secondary Source

Lancet Respiratory Medicine

Source Reference: Peiffer-Smadja, Yazdanpanah Y "Nebulised interferon beta-1a for patients with COVID-19" Lancet Respir Med 2020; DOI: 10.1016/S2213-2600(20)305.

https://www.medpagetoday.com/infectiousdisease/covid19/89636

FDA Oks Lantheus prostate cancer AI solution on GE Healthcare platform

• The FDA has granted 510(k) clearance for the use of Lantheus’  (LNTH +3.2%) artificial intelligence enabled automated bone scan index (aBSI) product on GE Healthcare’s Xeleris platform. The AI platform automates the detection of hotspots in bone indicative of metastatic disease and calculate the aBSI.
• In October 2019, the Company entered into a global software licensing agreement with GE Healthcare for the rights to aBSI.
• Under the terms of the non-exclusive agreement, GE Healthcare acquired from Lantheus the software license for aBSI for integration into its Xeleris platform, excluding the use of aBSI in Japan. Under the agreement with GE Healthcare, Lantheus will receive tiered licensing fees per license sold.
• https://seekingalpha.com/news/3636189-fda-oks-lantheus-ai-solution-for-prostate-cancer-on-ge-healthcare-s-platform