ENLV
Allocetra™ is being developed as an adjunctive therapy for preventing organ failure and mortality in sepsis, in combination with existing antibiotics agents
Favorable safety profile demonstrated across 140+ patients
Management team with a track record of creating shareholder value and getting drug products through marketing approvals globally in multi-billion dollar market segments
First patient dosed with AllocetraTM in thumb osteoarthritis, a degenerative, debilitating and progressive disease that affects millions of people-Thumb osteoarthritis currently has no FDA-approved therapy and no effective long-term treatment
CHECK OUT THE INVESTOR PRESENTATION HERE
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Hello Everyone,
Yesterdays profile continued to trade in the green after it was up double digits on strong interest during the session, 2 days in a row.
It broke yesterdays highs and ran through .42 during trading today.
We wanted to bring another company to your attention before the end of the week.
Pull up ENLV immediately.
This is a company that we have yet to feature on this newsletter.
Enlivex is at an advanced clinical stage, with Phase IIb trials for sepsis showing promise for a $33 billion market opportunity and Phase I/II trials in osteoarthritis aiming at a combined market opportunity of $9 billion. Additionally, the prospect of a short regulatory approval pathway in Europe for its sepsis treatment enhances the value proposition for investors. Enlivex's strong leadership team, proven by their successful $560 million exit event with PROLOR Biotech and a significant partnership with Pfizer, underscores the company's potential for high returns. With a robust cash balance and plain vanilla capital structure ensuring operational runway through the end of 2025 and a buy recommendation with a $12 per share price target, Enlivex stands out as a promising investment for investors seeking to capitalize on the next wave of innovations in immunotherapy and cell reprogramming technologies.
Allocetra™ is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra™ has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening and life-debilitating clinical indications that are defined as “unmet medical needs.”
While 55% of Americans have never heard of sepsis, it is the third leading cause of mortality in the United States following heart disease and cancer.
Sepsis is a highly heterogeneous syndrome that is caused by an unbalanced immune host response to an infection. The first use of the term ‘sepsis’ in a medical context was probably in poems by Homer that date from more than 2,700 years ago, but sepsis was not clinically defined until the early 1990s when a group of key opinion leaders released the first consensus definition of sepsis.
Herein, sepsis was defined as a systemic inflammatory response syndrome (SIRS) caused by an infection; increasing severities were designated ‘severe sepsis’ (referring to sepsis and organ dysfunction) and ‘septic shock’ (referring to sepsis and refractory hypotension).
In the most recent ‘Sepsis‑3’ consensus definition, sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection, and the term severe sepsis has been removed.
Of note, although infection is the triggering event in this definition of sepsis, the aberrant immune response often remains after successful treatment of the infection. Sepsis clearly imposes a substantial global burden in terms of morbidity and mortality. Nearly all patients with severe sepsis require treatment in an intensive care unit (ICU).
Sepsis, which has been identified by the World Health Organization (WHO) as a global health priority, has no proven pharmacologic treatment other than appropriate antibiotic agents, fluids, and vasopressors as needed. Reported death rates among hospitalized patients range between 30% and 45%, and one out of three patients who died in a U.S. hospital had Sepsis.
CLINICAL STATUS
On March 18, 2020, the Company announced the final safety and efficacy data from the Company’s completed Phase Ib. The final analysis compared the clinical data of 10 patients admitted to the intensive care unit with sepsis who were administered Allocetra™ upon their admission, with 37 patients who were matched controls (matched by age, gender, Sequential Organ Failure Assessment (SOFA) score, and infection source) who received only the standard of care treatment at the same hospital during 2014-2019 but did not receive Allocetra™. The clinical trial was conducted at Hadassah Medical Center, which is one of the largest and most prestigious hospitals in Israel (“Haddasah”). The Acute Physiology and Chronic Health Evaluation (APACHEII) score of the Allocetra™-treated group was 12.3, and the corresponding probability of mortality of at least one patient in that group was predicted at 85% based on the hospital’s ICU staff’s clinical assessment of each patient’s overall condition at admission. However, none (0%) of the Allocetra™-treated patients died during the 28-day study period, as compared to 27% 28-day mortality in the matched controls group. Each of the 10 Allocetra™-treated patients had between 2 to 5 dysfunctional organ systems upon admission to the ICU. All (100%) of the Allocetra™-treated patients had rapid and complete recovery from their septic conditions and of any organ dysfunction that was present upon admission to the ICU. Despite the similarity of organ-failure state (SOFA) at entry between the Allocetra™-treated patients and the matched controls group (average of 3.4 versus 3.47), not a single patient treated with Allocetra™ had any increase in organ-failure state post administration of Allocetra™, while the majority of the patients in the matched controls group had an increase in organ-failure state. The average worsening in organ-failure state of patients in the matched controls group was approximately 100% compared with their ICU hospitalization state vs zero (0%) percent worsening in organ-failure state of Allocetra™-treated patients post administration of Allocetra™ (p< <0.0001). The ICU length-of-stay for all Allocetra™-treated patients was significantly shorter than those patients who received only the standard of care, with an average of 4 days compared to 11.11 in the matched controls group, a 64% reduction (p<0.0001). The slowest ICU discharge of a patient treated with Allocetra™ was after 8 days, while approximately 50% of the matched controls group were still at the ICU after 28 days. Allocetra™ was shown to be safe and tolerable, with no serious unexpected severe adverse reactions and no serious adverse events.
Summary of Planned Clinical Trials of Allocetra™ for the treatment of Organ Dysfunction and Failure Associated with Sepsis
In light of the encouraging results of the Phase Ib in patients with severe sepsis, the Company has initiated a Phase II clinical trial, which is currently ongoing. The company intends, subject to clinical trial outcomes, to submit a conditional marketing authorization application to EMA for this indication.
Enlivex Announces the Dosing of the First Patient in a Randomized, Placebo-Controlled Phase I/II Trial Evaluating AllocetraTM in up to 46 Patients with Thumb Osteoarthritis
PUBLISHED
JUN 24, 2024 8:00AM EDT
- First patient dosed with AllocetraTM in thumb osteoarthritis, a degenerative, debilitating and progressive disease that affects millions of people
- Thumb osteoarthritis currently has no FDA-approved therapy and no effective long-term treatments
Ness-Ziona, Israel, June 24, 2024 (GLOBE NEWSWIRE) -- Enlivex Therapeutics Ltd.(Nasdaq: ENLV, the “Company”), a clinical-stage macrophage reprogramming immunotherapy company, today announced that the first patient has been dosed in an investigator-initiated, randomized, placebo-controlled Phase I/II trial evaluating the efficacy and safety of Allocetra™ following injection into patients with basal thumb joint (first carpometacarpal (CMC) joint) osteoarthritis, for which conventional therapies have failed.
This investigator-initiated Phase I/II trial plans to recruit up to 46 patients and is composed of two stages. The first stage is a safety run-in, open-label dose escalation phase to characterize the safety and tolerability of an AllocetraTM injection in patients with osteoarthritis of the first basal thumb joint (first CMC joint) of the target thumb to identify the dose for the randomized stage. The second stage is a double-blind, randomized, placebo-controlled stage, which the Company expects to initiate following the completion of the safety run-in stage and selection of the safe and tolerable dose. Up to 40 patients will be randomized in a 1:1 ratio for treatment with either AllocetraTM at the selected dose or placebo. The primary safety endpoint will measure the frequency and severity of adverse events and serious adverse events, and the efficacy endpoints will include assessments of change from baseline in pain and function for up to 12 months following treatment.
“This is the first injection of AllocteraTM into the basal thumb joint, and we are pleased with the swift enrollment of the first patient just a few weeks following regulatory approval to initiate this trial. The injection of AllocteraTM into the patient’s basal thumb joint was successfully completed with no complications.” stated Oren Hershkovitz, Ph.D., CEO of Enlivex.
ABOUT BASAL THUMB OSTEOARTHRITIS
Osteoarthritis of the thumb is a chronic condition causing pain, stiffness and occasional clicking and swelling in the joint at the base of thumb (also known as the carpometacarpal or CMC joint). Simple daily tasks can become painful and difficult. The prevalence of thumb osteoarthritis increases substantially with age and is more common in postmenopausal woman. The prevalence of radiographic base thumb OA was reported to be 5.8% and 7.3%, for 50-year-old males and females, respectively, while the respective prevalence for 80-year-old male and female participants was reported as 33.1% and 39.0%1. The overall estimated symptomatic prevalence is up to 15% in adults over 30 years of age2. Osteoarthritis of the thumb is a degenerative and progressive condition, and over time, conservative treatments and anti-inflammatory medication to reduce pain and swelling start losing their effectiveness. Currently, there are no effective long-term treatments for this disease.
Enlivex Announces Topline Results of Its Phase II Trial Evaluating Allocetra™ In Patients With Sepsis
PUBLISHED
APR 11, 2024 8:05AM EDT
- Analysis of eligible1 patients from the sepsis Phase II study (NCT# NCT04612413)
- In accordance with the study protocol, the safety and efficacy topline analysis includes sequential organ failure assessment (SOFA) scores and mortality for the 28-day period post treatment.
- Efficacy:
- Stand-alone analysis of the Allocetra™-treated patients, of which 78% had septic shock and 65% had invasive ventilation at screening, demonstrated substantial reductions in SOFA scores and 65% reduction in overall mortality rate as compared with expected mortality2. By day 28, the analysis showed 90% reductions of SOFA scores for sepsis patients whose infection source was urinary tract, 68% for patients whose infection source was community-acquired pneumonia, and 36% for patients whose infection source was internal abdominal infection.
- Relative analysis demonstrates a potential indication of effect of Allocetra™ as compared with placebo in high-risk, severe sepsis patient population (organ failure scores >=7), originating from urinary tract infections (“High Risk UTI”). Enlivex intends to consider a potential follow-on, randomized, controlled study of a solely High Risk UTI sepsis population. Up to 31% of sepsis cases start as urinary tract infections, representing up to 9.8 million cases in the United States and Europe, leading to as many as 1.6 million deaths3, and represents a substantial potential market opportunity for Allocetra™.
- The study was designed for patients to be randomized with equal degree of SOFA scores across treatment and placebo groups. The randomization resulted in the Allocetra™-treated cohorts having 20% higher frequency of septic shock and 35% higher frequency of invasive ventilation prior to treatment, as compared with the control group. Both of these patient attributes are associated with a significantly higher degree of difficulty of treatment and higher mortality rates. These imbalances made it challenging to deduce the relative effect in other patient subgroups.
- Safety: Stand-alone and placebo-compared analysis across all sepsis patient subgroups and risk categories demonstrated acceptable safety and tolerability profile of Allocetra™ IV infusions.
Nes-Ziona, Israel, April 11, 2024 (GLOBE NEWSWIRE) -- Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the “Company”), a clinical-stage macrophage reprogramming immunotherapy company, today announced positive indication of effect and safety results from its Phase II study of Allocetra™ in patients with sepsis, in which 120 patients enrolled. Bruno François, M.D., intensive care physician, is the head of the Limoges Clinical Investigation Center (Limoges, France). Dr. François took a primary role in the design of the study, medical support and oversight of patient eligibility. Dr. François was the national coordinator for numerous emergency trials, especially in sepsis, and has participated in several advisory boards for sepsis multinational trials, independent clinical evaluation committees and adjudication committees. Dr. François stated, “I am very excited about Allocetra’s™ novel approach, using a first-in-class innovative cell therapy to explore the treatment of patients with acute, life-threatening sepsis and septic shock. The study, a randomized controlled trial conducted in six countries and multiple clinical centers, demonstrated a favorable safety profile for Allocetra™. Within the context of the study, we also learned the ease of use and feasibility to infuse Allocetra™ cells to patients even in the complex setting of the intensive care unit. The study was well designed and executed, although randomization resulted in the Allocetra™-treated cohorts having higher frequencies of septic shock and invasive ventilation prior to treatment, as compared with the control group. Because these patient attributes are typically associated with a significantly higher degree of difficulty of treatment and higher mortality rates, the relative effect of Allocetra™ in some patient sub populations was challenging to deduce. I am pleased with the unusually low mortality rates across the board in the study, and that Allocetra™ demonstrated a potential indication of effect in high-risk sepsis patients originating from urinary tract infections. A substantial number of sepsis cases originate from urinary tract infections, and we have been actively searching for additional treatment alternatives for those patients, especially those who are at high risk. Having reviewed the topline study results, I look forward to reviewing the forthcoming additional safety and biomarker data of patients in the study, and I recommend the further exploration of the use of Allocetra™ in the High Risk UTI population.”Oren Hershkovitz, Ph.D., CEO of Enlivex said, “We are pleased with the demonstration of substantial SOFA score reductions and low mortality rate of the Allocetra™-treated patients across all origins of sepsis in the study, the indication of effect compared with placebo for the high-risk patients whose sepsis originated from urinary tract infections, and the favorable safety profile of Allocetra™. The Company intends to consider, upon reviewing the totality of the data, a potential follow-on, randomized, controlled study of a solely High Risk UTI sepsis population. Up to 31% of sepsis cases start as UTIs4, and this represents a substantial potential market opportunity for Allocetra™. The randomization resulted in the Allocetra™-treated cohorts having 20% higher frequency of septic shock and 35% higher frequency of invasive ventilation prior to treatment, compared with the placebo group. Both of these patient attributes are associated with significantly higher degree of difficulty of treatment and higher mortality rates, and potentially resulted in patients with more severe sepsis in the Allocetra™-treated cohorts. These biases made it challenging to deduce the relative effect in other patient subgroups.”
ABOUT UTI Urinary tract infection (UTI) is the second most common infectious disease affecting more than 150 million people globally annually. Up to 31% of sepsis cases start as UTIs, representing up to 9.8 million cases in the United States and Europe, leading to as many as 1.6 million deaths4.
ABOUT THE PHASE II SEPSIS CLINICAL TRIAL (NCT# NCT04612413) The Phase II trial was a placebo-controlled, randomized, dose-finding, multi-country, multi-center study, evaluating frozen-formulation Allocetra™ in addition to standard of care in patients with sepsis associated with pneumonia, biliary, urinary tract, or peritoneal infections. The results contained in this press release represent topline data and are subject to revision based on the ongoing collection of study information and detailed analysis. The Company expects to release further details about the study in a forthcoming presentation.
ABOUT ALLOCETRA™ Allocetra™ is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra™ has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents.
NEWS
MANAGEMENT
Sincerely,
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