Primary endpoint data shows 12-month overall response rate (ORR) of 33.6%
Biologics license application (BLA) submission intended for 2H 2024; first patient expected to be enrolled in IGNYTE-3 confirmatory trial in Q3 2024
Company to host conference call and webcast today at 8:00 a.m. ET
Replimune will host a conference call and webcast today at 8:00 a.m. ET. Listeners can register for the conference call via this link. Analysts wishing to participate in the question-and-answer session should use this link. The webcast and slides of the presentation can be accessed in the Investors section of the Company’s website at www.replimune.com. A replay of the webcast will be available on the Company’s investor website approximately two hours after the call's conclusion. Those who plan on participating are advised to join 15 minutes prior to the start time.
remains on track to report key outcomes later in July.
Pepinemab targets astrocyte reactivity and neuroinflammation, believed to be key drivers of neurodegeneration.
What can we expect to learn from this study?
Vaccinex scientists discovered and published that SEMA4D, a molecule that binds to high affinity plexin-B1 receptors predominantly expressed on astrocytes in the brain, is highly upregulated on stressed or damaged neurons during progression of Alzheimer’s Disease (AD).
Astrocytes, which are key brain cells that support the health and function of neurons, undergo substantial changes in morphology and gene expression when SEMA4D binds to their plexin-B1 receptors. As a result, they switch from normal supportive functions to neurotoxic inflammatory activity that is believed to accelerate and aggravate progression of AD.
The Company’s hypothesis, which is being tested in the SIGNAL-AD study, is that treating with pepinemab antibody can block signaling by SEMA4D and prevent some or all the damaging consequences of astrocyte activation.
The Company has previously reported that antibody blockade of SEMA4D appears to protect and restore healthy astrocyte functions and to slow or prevent disease progression in patients with Huntington’s disease by several different measures.
Key outcomes of the SIGNAL-AD study will include safety and tolerability and the impact of pepinemab treatment on brain metabolic activity as detected by FDG-PET and astrocyte reactivity reflected in plasma levels of glial fibrillary acidic protein (GFAP), a molecule known to be released into blood by reactive astrocytes. Together, these are key biomarkers of disease progression.
Deposition of Aβ amyloid in the brain is considered to be the earliest recognized event in the pathologic cascade leading to AD. Aggregates of Aβ are believed to trigger a series of subsequent events, including astrocyte reactivity and formation of toxic tau tangles in neurons, which are believed to be key drivers of neurodegeneration. Accordingly, secondary endpoints will also include plasma levels of phosphorylated tau peptide (p-tau 217), a biomarker released into blood during formation of tau tangles in neurons. In addition, several validated cognitive scales will be employed as exploratory endpoints to evaluate potential treatment effects on cognitive decline, the main clinical symptom of AD.
The Company believes that the prevalence of AD (6 million people diagnosed with AD in the US alone) and current concerns about the limitations of treatment with anti-Aβ amyloid antibodies such as Leqembi (Eisai and Biogen) and donanemab (Eli Lilly) could make pepinemab, if approved, attractive as a potential alternative treatment or possibly for use in combination with anti-Aβ to enhance the benefit to patients. Pepinemab has, to date, been well-tolerated in clinical trials that enrolled a total of more than 600 patients.
PICCOLO trial met its primary endpoint of objective response rate (ORR)
Data from the study will be presented at a future medical meeting
AbbVie (NYSE: ABBV) announced today positive topline results from the Phase 2 PICCOLO trial evaluating investigational mirvetuximab soravtansine (ELAHERE®) monotherapy in heavily pre-treated patients with folate receptor-alpha (FRα) positive, platinum-sensitive ovarian cancer (PSOC). The study met its primary endpoint with an objective response rate (ORR) of 51.9% (95%CI 40.4 – 63.3%).
In addition, the median duration of response (DOR), a key secondary endpoint, was 8.25 months.
The safety profile of mirvetuximab soravtansine was consistent with findings from previous studies, and no new safety concerns were identified. Full data from the PICCOLO study will be presented at a future medical meeting.
Two BLS reports, one monthly, the other quarterly highlights a 3.4 million overstatement in the monthly jobs reports.
BLS QCEW vs BLS CES (Current Employment Statistics, the Monthly Nonfarm Payroll Job Report) Chart by Mish
Understanding the Chart
Nonfarm Payrolls are are from the Establishment Survey (CES). The sample survey was 666,000 individual worksites in 2023.
QCEW (Quarterly Census of Employment and Wages) is a count of Unemployment Insurance (UI) administrative records submitted by 11.9 million establishments.
QCEW is quarterly, within five months after the end of each quarter. The CES survey is monthly. For the comparison, I used end-of-quarter totals for CES.
SA means seasonally adjusted. NSA means not seasonally adjusted.
QCEW is a survey of 11.9 million establishments vs 666,000 for CES.
QCEW shows strong seasonal tendencies. Thus, it’s a mistake to compare seasonally adjusted CES (light blue line in the above chart) to QCEW.
It’s clear the monthly nonfarm payrolls are overstated every month. It looks random if you make the mistake of comparing SA data to NSA data. Here’s the correct application.
Nonfarm Payrolls NSA Minus QCEW
QCEW data is not in a friendly format to download. I manually plugged in the above quarterly numbers from a QCEW download into a better formatted CES download from the St. Louis Fed.
In normal times, neither heading into or out of recessions, the differences seem to vary randomly in a tight range.
At economic turns, the variance is much wider with a caveat that I only went back to 2019.
Understanding the Discrepancies
If the difference was nearly constant, say ~2.5 million, it would not matter. But if sharply increasing or decreasing numbers happen near recessions, the discrepancies do matter.
Comparing NSA numbers, Nonfarm payrolls are 3.42 million higher than QCEW numbers. That is the largest difference since 3.46 million at the height of the Covid pandemic.
The only other 3+ million difference was in the third quarter of 2020.
One more comparison will put things into proper perspective.
2022 Q4-2023 Q4 CES vs QCEW
CES: 155,211,000 to 158,269,000 (+3.06 million)
QCEW: 152,525,000 to 154,848,000 (+2.32 million)
CES reports 32 percent more job gains in 2023 vs QCEW!
Jobs Report on Friday
The monthly jobs report is Friday. The Bloomberg consensus estimate is 188,000 jobs.
I’ll take the under.
Regardless, whatever number the BLS reports is highly likely to be revised lower.
On Wednesday, the stocks ofMadrigal Pharmaceuticals IncMDGLandSagimet Biosciences IncSGMTare trading lower.
At the EASL International Liver Congress 2024, Eli Lilly And CoLLY shared an abstract highlighting fibrosis results from a Phase 2 trial of tirzepatide in patients with metabolic dysfunction-associated steatohepatitis (MASH).
Other companies working on MASH candidates include 89bio Inc ETNB, Akero Therapeutics IncAKRO, and Viking Therapeutics IncVKTX.
The Phase 2 SYNERGY-NASH trial studied three doses (5 mg, 10 mg or 15 mg) of tirzepatide in 190 people. End-of-treatment liver biopsies were available for 157 participants.
The proportion of participants who achieved MASH resolution without worsening of fibrosis was 9.8% for placebo, 43.6% for 5 mg, 55.5% for 10 mg and 62.4% for 15 mg.
Among 155 participants who completed the study on treatment with evaluable biopsies, the primary endpoint of MASH resolution without worsening of fibrosis was achieved by 51.8%, 62.8%, and 73.3% for tirzepatide 5 mg, 10 mg, and 15 mg, respectively, compared with 13.2% for placebo.
The proportion who achieved ≥ 1-stage fibrosis improvement without worsening of MASH was 29.7% for placebo, 54.9% for tirzepatide 5 mg, 51.3% for tirzepatide 10 mg, and 51.0% for tirzepatide 15 mg.
A reduction in nonalcoholic fatty liver disease activity score (NAS) by ≥ 2 points was achieved by 71.7% to 78.3% of participants across the three tirzepatide dose groups and by 36.7% with placebo. Body weight was reduced by up to 17.3% with tirzepatide.
Liver enzymes and fat decreased, and serum and imaging biomarkers of liver inflammation and fibrosis significantly improved in the tirzepatide groups compared to the placebo.
The abstract added that there was a lack of a clear dose relationship in achieving MASH resolution without worsening the fibrosis endpoint.
Larger and longer trials are needed to assess the efficacy and safety of tirzepatide for non-cirrhotic MASH.
U.S. National Institutes of Health haslaunchedtwo clinical trials to examine a novel long-acting form of HIV pre-exposure prophylaxis (PrEP) in cisgender women and people who inject drugs.
The mid-stage studies will assess the safety, acceptability, and pharmacokinetics (how a drug moves through the body) of lenacapavir, an antiretroviral drug administered by injection every six months.
Gilead Sciences Inc.GILD sponsored and funded the studies implemented through the HIV Prevention Trails Network (HPTN).
The HPTN is supported by grants from the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID), with scientific collaboration on this study and others from the National Institute on Drug Abuse (NIDA) and co-funding from NIDA and other NIH institutes.
FDA has already approved Lenacapavir for HIV treatment, in combination with other antiretroviral therapy, of heavily treatment-experienced individuals.
Lenacapavir is the first long-acting injectable to be offered with administration just once every six months.
Cisgender women—people who self-identify as female and were assigned female sex at birth—and people who inject drugs accounted for 18% and 7% of new HIV diagnoses in the United States in 2021, respectively.
The first trial will enroll cisgender women, with a focus on making enrollment accessible to women who self-identify as Black and/or Latina.
The second trial will enroll a diverse group of people who inject drugs.
In both studies, participants will be randomly assigned to receive either injectable lenacapavir or an FDA-approved PrEP formulation consisting of oral tenofovir disoproxil fumarate and emtricitabine.
"At time when some of our adversaries aim to undermine our ties with our greatest ally, we only further strengthen our alliance," Defense Minister Yoav Gallant announced Tuesday uponunveilingIsrael's signing a new $3 billion deal with Lockheed Martin for 25 F-35 fighter jets.
"This sends a powerful message to our enemies across the region," he continued. This will add a third squadron of the advanced stealth fighters to the Israeli air force arsenal.
"The delivery of the aircrafts to the IDF (army) will commence in 2028 at a rate of three to five aircrafts per year," the defense ministry specified in a statement.
Once the contract is eventually fulfilled, this will bring the total number of F-35s in Israel's fleet to 75. Israel remains the only country in the Middle East to possess them. The deal was first introduced last summer, when the defense ministry said it was pursuing talks with the US over the transfer.
The newly inked contract underscores Washington's long-term commitment to Israel's defense and maintaining complete military technological superiority over enemies and rivals in the region, despite current tensions among the allies over the proposed Gaza ceasefire deal.
As we detailed previously, Israel was the first foreign recipient of the F-35, also known in the US as the Joint Strike Fighter and in Israel by its Hebrew name "Adir." Israel first used the F-35 in combat when it bombed Syria in 2018.
"The F-35 squadron has become an operational squadron," Maj. Gen. Amikam Norkin said at the time. "We are flying the F-35 all over the Middle East – we might be the first to attack with F-35 in the Middle East," he said.
Israel now uses these advanced fighters to regularly attack Syria, often firing from above Lebanese airspace. It has been able to attack what regional media often calls 'Iranian assets' in Syria with impunity.
Already in 2024, Israel has attacked Syria over 40 times, most often in the south of the country - in and around the capital of Damascus.
Israel had for much of the last decade also covertly supported the US-Gulf regime change war against the Syrian state which had the aim of toppling President Bashar al-Assad
