FDA Clears Pluristem’s IND Application for Phase II COVID-19 Study

• 140 patients with severe COVID-19 and ARDS to be treated
• Primary endpoint: ventilator free days during the main 28-day study period, secondary endpoint includes survival rate and ICU free days

Pluristem Therapeutics Inc. (Nasdaq:PSTI) (TASE:PSTI), a leading regenerative medicine company developing a platform of novel biological therapeutic products, announced today that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for a Phase II study of its PLX cells in the treatment of severe COVID-19 cases complicated by Acute Respiratory Distress Syndrome (ARDS). The study, titled “A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Phase II Study to Evaluate the Efficacy and Safety of Intramuscular Injections of PLX-PAD for the Treatment of severe COVID-19” will treat 140 adult patients that are intubated and mechanically ventilated and are suffering from respiratory failure and ARDS due to COVID-19. The primary efficacy endpoint of the study is the number of ventilator free days during the 28 days from day 1 through day 28 of the study.

The objective of the study is to evaluate the efficacy and safety of one or two intramuscular (IM) injections, in three different dosages, of PLX-PAD for the treatment of ARDS resulting from COVID-19. The primary endpoint determination will be performed at the end of the 28 day main study period. Safety and survival follow-up will be conducted at week 8, 26 and 52. Pluristem has been treating patients suffering from severe complications caused by COVID-19, such as ARDS and inflammatory complications, in the U.S. and Israel through compassionate use programs. Preliminary data from these compassionate use programs in Israel was reported on April 7, 2020. A Clinical Trial Authorization (CTA) has also been filed in Europe for a Phase II COVID-19 trial, with the first European clinical sites planned in Germany and Italy.

“We are very pleased to gain clearance to commence our Phase II COVID-19 study in the U.S. We are shifting gears now with a main focus on a rapid initiation of the clinical trial, leveraging our technological and logistical competitive advantages developed through our clinical trial experience in the U.S. and Europe.  We believe we can complete enrollment quickly and we expect to provide guidelines on the expected study duration a few weeks following the commencement of the study,” stated Pluristem CEO and President, Yaky Yanay. “In the last few weeks, we have received dozens of applications from physicians and families seeking to participate in the Expanded Access per patient program. We look forward to working with hospitals and physicians on a larger scale to deliver our PLX cells, through an off-the-shelf, easy to use PLX cell product candidate, which may potentially accelerate recovery time from life threatening conditions, and to improve survival, in the most severe COVID-19 cases.”

https://www.biospace.com/article/releases/u-s-fda-clears-pluristem-s-ind-application-for-phase-ii-covid-19-study/

Macrogenics scoops its Asco bounce

A tiny glimpse at very early data has more than tripled Macrogenics’ market cap. The pressure is now on to confirm these signals.

Macrogenics yesterday managed to achieve an early Asco bounce, providing a sneak peek at some data that will be presented at the annual cancer conference – a week before abstracts are due to be released.
Very early data in three pipeline projects piqued interest, sending the stock soaring by a huge a 231% to a two-year high and adding around $750m to the company’s market cap. This is quite a rise for updates described as “directionally encouraging” by the typically bullish sellside, and investors who piled in will have to hope that further details support this reaction.
Some extra information should emerge in the Asco abstracts, due to be released on May 13, before full details at the conference that starts at the end of month. But it should be remembered that these impending updates will be very early takes on the efficacy of these projects.

More than margetuximab? The Macrogenics pipeline
Project	Mechanism	Detail
Filed
Margetuximab	Anti-Her2 MAb	H2 2020: final OS from Sophia breast cancer trial and first data from 1L gastric trial, Mahogany
Phase III
Retifanlimab (MGA012)	Anti-PD-1 MAb	Licensed to Incyte; first data from potentially registrational anal cancer study due H2 2020
Phase I/II
Flotetuzumab	Anti-CD123 T-cell engaging bispecifc MAb	Some trials halted owing to Covid-19; update on filing plans in AML due Q2 2020; further data at ASH 2020
MGD013	Anti-Lag3 & PD-1 bispecific MAb	Ph1 solid tumour data at Asco; 40% ORR seen in Her2+ tumours
Enoblituzumab	Anti-B7-H3 MAb	Start of H&N phase 2 delayed by Covid-19
MGD019	CTLA 4 & anti-PD-1 bispecific MAb	4 responses in 13 evaluable patients, various tumours, at ≥3mg/kg
MGC018	Anti-B7-H3 ADC	PSA reduction of ≥50% in 5 of 7 mCRPC patients; phase I data at Asco
No update yesterday, and no longer listed in pipeline on website
MGD007	Anti-gpA33 T-cell engaging bispecific MAb
MGD009 (orlotamab)	Anti-B7-H3 T-cell engaging bispecific MAb	Was on clinical hold owing to liver tox
MGD014	Anti-HIV bispecific MAb
Source: EvaluatePharma, company statements.

One of the main Asco presentations concerns the B7-H3 antibody-drug conjugate MGC018, which is apparently showing promise in prostate cancer. Reductions in PSA of 50% or more were seen in five of seven patients with metastatic castration-resistant disease, Macrogenics disclosed yesterday, and the company plans a dose-expansion cohort in this tumour.
This equates to a 71% response rate on this measure, nearly as good as the impressive results generated by Xtandi in mCRPC: one cut of the Prevail trial found that 80% of patients achieved PSA declines of ≥50%, although of course the subject numbers differ enormously.
B7-H3 is highly expressed on most solid tumours and in particular prostate cancer; the ongoing phase I trial is being conducted in various tumours, and activity has been seen elsewhere, Macrogenics said.
The second Asco presentation of note will involve the Lag3/PD-1 bispecific MGD013. Yesterday, the company teased a 40% ORR seen in “over a dozen” patients with Her2-positive tumours, who were treated with ’013 and margetuximab, Macrogenics’ Her2-targeting antibody. Targeting PD-1 and Her2 has previously only managed to achieve response rates of 0-15%, the company claimed, adding that development of ’013 plus margetuximab would now be prioritised.
MDG013 is in a large phase I solid tumour study, and activity is being seen across several tumour types, including after anti-PD-1 therapy, the company said. Data on this should also be at Asco.
Other shots
Not slated for Asco but also discussed yesterday was MGD019, a bispecific that hits PD-1 and CTLA4 in a large phase I basket study in various advanced solid tumours, where dose escalation has been completed. The company disclosed that of 13 evaluable patients treated at ≥3mg/kg, four responses have been seen, albeit one unconfirmed, in four tumour types.
Macrogenics expect to take forward a much higher dose, which is important because, as Stifel analysts point out, this far exceeds the equivalent doses at which Opdivo and Yervoy are used. According to Macrogenics, dose limiting toxicities were not seen with ‘019, with the project’s safety profile described as “quite favourable”.
Notably, Astrazeneca has put its weight behind a bispecific approach to get the most out of this combination, and further data on ’019, due to emerge later this year, becomes an important event (Astra turns to bispecifics to solve the treme problem, February 14, 2020).
Dwindling hopes for the potential of margetuximab, Macrogenics’ most advanced project, have beaten down the company’s stock since over the past 12 months. A final look at overall survival towards the end of the year will determine the project’s future, as will the approaching regulatory review of the data.
Data in gastric cancer might salvage the project; objective responses were observed in three of four evaluable patients recruited into the first-line Mahogany trial, the company said yesterday. The plan is to seek accelerated approval on this initial single-arm data, though again these early hints could yet prove misleading.
If yesterday’s presentation was designed to prove that Macrogenics is about more than margetuximab it certainly worked. However, for share price gains to prove durable these hints of clinical activity must also prove robust.
https://www.evaluate.com/vantage/articles/news/trial-results/macrogenics-scoops-its-asco-bounce

Healthcare jobs declined by 1.4M in April as physician practices shed 243,000 jobs

The number of healthcare jobs declined by 1.4 million in April, led by a major decline in jobs in physicians’ and dentists’ offices, according to government figures.
The healthcare sector has been slammed by the COVID-19 pandemic due to a steep drop in patient volume. Hospitals have also been hit hard financially by the cancellation of elective procedures, which may resume.
The data from the Bureau of Labor Statistics released Friday found dentists’ offices had the most losses with 503,000. Physicians’ offices lost 243,000, and other healthcare practices had 205,000 losses.

Overall, the unemployment rate for the U.S. rose from 10.3% to 14.7%, the highest monthly increase in the history of the federal government’s monthly jobs reports.

The employment data are the latest piece of evidence to underscore the massive financial crisis facing primary care physicians and hospitals.
A recent survey found 89% of clinicians reported large decreases in patient volume, and another 57% say less than half of their visits in the last week could be reimbursed.
The Trump administration has given physicians and healthcare workers more flexibility to adopt telehealth, and use of the practice has exploded.
But key questions remain about reimbursement, especially from commercial payers.
President Donald Trump has signed into law $175 billion in funding to help providers, but some groups say much more is needed to plug the massive hole created by COVID-19.
https://www.fiercehealthcare.com/practices/healthcare-jobs-declined-by-1-4-million-april-as-physician-practices-shed-243-000-jobs

9 states performing enough COVID-19 tests to reopen safely – Harvard institute

The U.S. needs to perform 900,000 COVID-19 tests per day to safely phase out social distancing measures, according to projections released May 7 by Harvard’s Global Health Institute.
The newest projection of testing need is a big jump from its earlier projection, which indicated the U.S. needed to process 500,000 to 600,000 tests per day to lift restrictions by June. The testing estimates increased because the latest modeling shows more people getting infected and dying of COVID-19 than previously projected, Ashish Jha, MD, director of the Harvard Global Health Institute told NPR.
On May 7, Harvard’s Global Health Institute published a simulation that estimates the testing needed by May 15 in each state. The amount of testing needed depends on several factors, including the size of the outbreak in each state, Dr. Jha told NPR. The following nine states are near or have exceeded the estimates of minimum testing needed: Alaska, Hawaii, Montana, North Dakota, Oregon, Tennessee, Utah, West Virginia and Wyoming.
Many of the states hardest hit by the COVID-19 pandemic, including New York, are far from the testing minimums estimated by Harvard.
Dr. Jha told NPR there are several caveats about the estimates, and the numbers should be used as a guide and not taken literally. Researchers also said testing alone is not enough. The model is built on the assumption that states are doing contact tracing and isolating infected or exposed people.
https://www.beckershospitalreview.com/public-health/9-states-performing-enough-covid-19-tests-to-reopen-safely-harvard-researchers-say.html

Covid-19 testing insufficient to resume elective surgeries – poll of hospitals

COVID-19 testing capacity in hospitals and surgery centers should be doubled before elective surgeries fully resume, a recent survey of 150 U.S. hospitals and surgery centers found.
The survey was conducted April 27-30 by Premier, a group purchasing organization.
Eighty-seven percent of the respondents said their facilities intend to test any patient admitted for an elective procedure for COVID-19, but only 27 percent said they were currently able to do so.
According to the survey, hospitals and healthcare facilities need to expand their current COVID-19 diagnostic testing capacity by at least 211 percent to even partially resume elective procedures and diagnostic services.
Of the respondents, 81 percent said they intend to screen all employees for symptoms of COVID-19 before resuming nonemergency procedures, but only 32 percent said they’d be able to give COVID-19 diagnostic tests to all of their front-line healthcare workers. Only 22 percent said they’re able to test all employees, including food service workers and janitors.
The survey indicates that shortages of reagents and testing swabs are the main barriers to more widespread testing.
Read the full survey here.
https://www.beckershospitalreview.com/supply-chain/coronavirus-testing-insufficient-to-resume-elective-surgeries-poll-of-hospitals-says.html

Meridian Bioscience Raises Guidance on Strength of COVID-19 Related Products

Meridian Bioscience, Inc. (NASDAQ: VIVO) today announced financial results for the second quarter ended March 31, 2020.
Second Quarter Fiscal 2020 Highlights:

• Consolidated Net Revenue of $57.3 million, up 14% year-over-year
• Life Science segment responded early and swiftly to the COVID-19 pandemic contributing to a record $22.4 million in revenues, up 33% year-over-year
• Diagnostics segment delivered over $34.9 million in revenue, the fifth consecutive quarter above $33 million and year-over-year growth for the first time in five quarters
• During the quarter, the Curian^® analyzer and HpSA^® assay received FDA clearance, the first internally developed new product in several years and the first of several in development

Jack Kenny, Chief Executive Officer, commented: “We had an extraordinary quarter on many fronts, led by our Life Science team’s rapid response to the COVID-19 pandemic.  Our raw materials were included in millions of molecular tests globally and soon will be in millions more rapid antibody tests.  Our Diagnostics segment delivered growth, soon to be supplemented with the contribution from our new Curian analyzer and assay.  Our strategic initiatives are setting the foundation for growth, and I am excited about what’s to come.”

Bryan Baldasare, Chief Financial Officer, commented: “Despite the turmoil of the COVID-19 pandemic, our financial position remains strong.  Demand for our Life Science products is unprecedented.  We have confidence in the direction of the business and are raising our guidance for the year.”

https://www.globenewswire.com/news-release/2020/05/08/2030293/0/en/Meridian-Bioscience-Reports-Second-Quarter-2020-Operating-Results-Raises-Guidance-on-Strength-of-COVID-19-Related-Products.html

Protagonist Therapeutics extends cash runway on focused plan for lead drug

Thinly traded micro cap Protagonist Therapeutics (NASDAQ:PTGX) is up 16% premarket on light volume on the heels of its announcement that it has chosen polycythemia vera, a type of blood cancer in which the bone marrow produces too many red blood cells, as the first indication for lead candidate PTG-300.

PTG-300 is a mimetic (“imitates” the action of) a natural peptide hormone called hepcidin that regulates iron absorption and utilization in the body and plays an essential role in the development of red blood cells.

The company says it is focusing its resources on this indication and has decided to defer the start of a Phase 2 study of PN-943 in ulcerative colitis which will reduce expenses and extend its cash runway an additional six months through mid-2022.

https://seekingalpha.com/news/3572151-protagonist-therapeutics-extends-cash-runway-on-focused-plan-for-lead-drug