Ovarest (leuprolide oral) / Enteris - LARVOL DELTA

EMBARK: A Phase 3 Randomized Study of Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in High-Risk Biochemically Recurrent Prostate Cancer (AIOM 2023) - "In pts with high-risk BCR, enza + ADT and enza mono demonstrated a statistically significant and clinically meaningful improvement in MFS vs pbo +ADT. The safety profile of enza was consistent with results from previous clinical studies."

P3 data

The struggle is real: Keeping up with the rapidly evolving clinical evidence in urology (Urology Times) - ""Keeping up-to-date is challenging, and rapid progress that is now occurring in our field is truly amazing," writes Michael S. Cookson, MD, MMHC, FACS. Like most of you, I appreciate data-driven approaches to medicine and try, when possible, to adhere to evidence-based medicine. Historically, well-constructed guidelines from trusted, reliable sources have helped provide a good reference for clinical guidance. And in what I will refer to as 'simpler' times, there seemed to be relatively close alignment between the published literature and the updated guidelines."

Online posting

PHARMACOKINETIC (PK) STUDY OF ORAL LEUPROLIDE DELIVERY WITH OVAREST® ACHIEVES DRUG LEVELS EXCEEDING THOSE OF APPROVED INJECTABLE PRODUCTS (ASRM 2022) - "Results confirm oral delivery of leuprolide levels expected to be within established therapeutic ranges. Leuprolide oral tablets in total daily doses from 80 to 120 mg appear to be safe, well tolerated, and roughly dose proportional. Compared to proprietary Enteris data and published historical data, Ovarest delivered more drug than highly effective injectable leuprolide formulations."

PK/PD data • Pain

Enteris BioPharma Presents Study of Ovarest Demonstrating Oral Delivery Comparable to or Exceeding Injectable Leuprolide (PRNewswire) - P=NA | N=NA | "The research detailed the results from a 22-patient study examining the pharmacokinetic (PK) profile and dose-proportionality of oral leuprolide compared to historical data for highly effective injectable leuprolide products. Results from the study confirmed that the oral delivery of leuprolide produced levels expected to be within established therapeutic ranges with Ovarest delivering more drug than highly effective injectable leuprolide formulations. Further, leuprolide oral tablets delivered in total daily doses from 80 to 120 mg appeared to be safe, well tolerated, and roughly dose proportional...Leuprolide is a gonadotropin-releasing hormone analogue that is used to treat endometriosis and uterine fibroids in women, prostate cancer in men..."

PK/PD data • Endometriosis • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Women's Health

Enteris BioPharma Announces Acceptance of Abstract for Oral Presentation at ASRM 2022 Scientific Congress & Expo (PRNewswire) - "Enteris BioPharma, Inc...announced today an abstract has been accepted for an oral presentation at the ASRM 2022 Scientific Congress & Expo being held Oct. 22-26, 2022 in Anaheim, Calif The abstract highlights research into the pharmacokinetics of an oral formulation of leuprolide developed utilizing Enteris' proprietary Peptelligence® platform, a novel formulation technology that enables oral delivery of molecules that are typically injected, including peptides and BCS class III and IV small molecules."

Clinical • Endometriosis • Women's Health

Enteris BioPharma Presents Data from Two Clinical Studies Involving Oral Formulations of Leuprolide at ENDO 2022 Annual Conference (Yahoo News) - "Enteris BioPharma, Inc...announced today that two posters describing clinical studies of oral formulations of leuprolide developed utilizing Enteris' proprietary Peptelligence® platform are being presented at the annual meeting of The Endocrine Society (ENDO 2022) taking place June 11-14, 2022, in Atlanta."

Clinical data • Endometriosis • Uterine Leiomyoma • Women's Health

Androgen Receptor Inhibition in CRPC: Part 1: Deciding Whether Next-Generation Scans Are Needed for nmCRPC (Targeted Oncology) - "During a live event, Evan Yu, MD, discussed how to monitor a patient being treated with androgen deprivation therapy and hormonal agents for nonmetastatic castration-resistant prostate cancer using prostate-specific antigen levels and next-generation imaging....PSMA-PET is newly FDA-approved 18F-DCFPyL [Pylarify] for staging of biochemical recurrence4 and gallium-68 gozetotide was [previously] FDA approved, with the University of California Los Angeles and University of California San Francisco having unlimited approval. Here in Seattle, we have a PSMA-PET imaging protocol, but you have to meet certain eligibility criteria. So, we have not been able to bill insurance companies for our PET imaging with PSMA-PET. We have not had [insurance] problems with fluciclovine F18 PET. I would say that more often than not, it goes through without issues for fluciclovine F18."

Media quote

Study to Evaluate the Pharmacodynamics and Efficacy of Leuprolide Tablets (Ovarest®) in Women With Endometriosis (clinicaltrials.gov) - P2 | N=16 | Recruiting | Sponsor: Enteris BioPharma Inc. | Not yet recruiting ➔ Recruiting | Initiation date: Nov 2021 ➔ Mar 2022

Enrollment open • Trial initiation date • Endometriosis • Gynecology

Study to Evaluate the Pharmacodynamics and Efficacy of Leuprolide Tablets (Ovarest®) in Women With Endometriosis (clinicaltrials.gov) - P2; N=16; Not yet recruiting; Sponsor: Enteris BioPharma Inc.

Clinical • New P2 trial • Endometriosis • Gynecology

Enteris BioPharma Announces Successful Completion of Phase 1 Clinical Trial of Optimized Peptelligence Oral Leuprolide (PRNewswire) - P1, N=22; "Enteris BioPharma, Inc...announced the successful completion of a Phase 1 clinical trial investigating its optimized Peptelligence oral tablet formulation of leuprolide. Data from the 22-patient study indicate that the optimized Peptelligence oral formulation is able to safely deliver a higher dose of leuprolide that enables blood concentrations comparable to subcutaneous or intramuscular depot injections."

P1 data • Trial completion • Endometriosis • Uterine Leiomyoma • Women's Health

CDK4/6 and PI3K Inhibitors for HR+/HER2- Breast Cancer in the Clinic Today: Thoughts From the Experts (Clinical Care Options) - "Joyce O'Shaughnessy, MD: There are several clinical trials currently investigating the use of CDK4/6 inhibitors in patients with HR+/ HER2- early breast cancer (EBC)....Sara Hurvitz, MD...: It was very interesting to see these data read out at the same time, but it was disappointing to see such discordant data, particularly since the data are very similar among the CDK4/6 inhibitors in the metastatic setting. There is preclinical evidence that the available CDK4/6 inhibitors are different: They have different potencies and different off-target effects."

Media quote

6 Questions About HR-Positive/HER-2-Negative Metastatic Breast Cancer Answered (Everydayhealth) - "While it means that your cancer has spread from the original tumor to other parts of your body, this subtype of invasive breast cancer tends to grow slowly and be less aggressive than other subtypes, according to Adam Brufsky, MD, PhD..."

Media quote

Carboplatin-pemetrexed in treatment of patients with recurrent/metastatic cancers of the head and neck; superior outcomes in oropharyngeal primaries. (PubMed) - "Combination carboplatin-pemetrexed is an effective and well-tolerated treatment, associated with a median PFS of 5.1?months and a clinical benefit in at least 57% of the patients treated."

Journal • Biosimilar • Esophageal Cancer • Head and Neck Cancer • Oncology

Hormone Therapy in Treating Patients Who Have Stage I or Stage II Prostate Cancer (clinicaltrials.gov) - P3; N=496; Active, not recruiting; Sponsor: M.D. Anderson Cancer Center; Trial primary completion date: Jun 2016 ->Jun 2017

Trial primary completion date • Biosimilar • Oncology • Prostate Cancer

Hormone Therapy in Treating Patients Who Have Stage I or Stage II Prostate Cancer (clinicaltrials.gov) - P3; N=496; Active, not recruiting; Sponsor: M.D. Anderson Cancer Center; Trial primary completion date: Jun 2015 ->Jun 2016

Trial primary completion date • Biosimilar • Oncology • Prostate Cancer

A Study of Pharmacokinetic/Pharmacodynamic Profile of Orally Administered Leuprolide in Healthy Female Volunteers (clinicaltrials.gov) - P2; N=32; Not yet recruiting; Sponsor: Enteris BioPharma Inc.; Initiation date: Sep 2016 ➔ Apr 2017; Trial primary completion date: Dec 2016 ➔ Jul 2017

Trial initiation date • Trial primary completion date • Biosimilar • Endometriosis

Regression of adenomyosis on MRI after a course of hormonal suppression in adolescents: A case series (ASRM 2011) - P=NA, N=4; Two of these patients underwent diagnostic laparoscopy that revealed enlarged uteri and no evidence of endometriosis; Both were symptomatically improved after monthly therapy with leuprolide acetate; Follow up MRI showed resolution of adenomyosis after six months in one patient and after three years in the other; The fourth patient had rapid resolution of symptoms and regression of adenomyosis on MRI one year after beginning leuprolide acetate

Retrospective data analysis

A comparison of progestogens or oral contraceptives and gonadotropin-releasing hormone agonists for the treatment of endometriosis: A systematic review (Expert Opin Pharmacother) - "Leuprolide was as effective as gestrinone, dienogest, and continuous oral contraceptives (OCs) for the relief of endometriosis-related pain, whereas it was superior to lynestrenol. Leuprolide was associated with a significant reduction in bone mineral density and estradiol levels and a higher incidence of hot flushes, headaches, mood changes, and vaginal dryness, whereas progestogens were associated with higher incidences of weight gain and acne."

Review • Endometriosis • Uterine Leiomyoma

Enteris CEO to discuss Overest endometriosis therapy at N.Y. Biotech Conference (Endometriosis News) - "Enteris BioPharma will discuss the potential of its oral peptide drug Ovarest (leuprolide tablet) to treat endometriosis at the upcoming 24th Annual Future Leaders in the Biotech Industry Conference."

Clinical • Endometriosis

Atorvastatin exerts anti-nociceptive activity and decreases serum levels of high-sensitivity C-reactive protein and tumor necrosis factor-α in a rat endometriosis model (Arch Gynecol Obstet) - "Atorvastatin treatment exhibited significant analgesic activity in hot plate model (P = 0.022). The serum hs-CRP and tumor necrosis TNF-α levels were similar between the Group 2 and Group 3 (P > 0.05); however atorvastatin caused significant decrease in both serum markers. The histological and immunohistochemical scores were also found to be markedly lower in Group 1 and Group 2 (P < 0.05)."

Preclinical • Endometriosis

Contraceptive effect of Uncaria tomentosa (cat's claw) in rats with experimental endometriosis (Acta Cir Bras) - Uncaria group presented nine samples (90%) with immature ovarian follicles, whereas the placebo group did not present any case and in the leuprolide group there were eight rats (88%) with the same change

Preclinical-animal

Companies to watch: Enteris BioPharma (Life Science Leader) - "Its lead product candidates are Ovarest (oral leuprolide tablet), in preparation for a Phase 2 trial in endometriosis later this year..."

Anticipated new P2 trial • Endometriosis