Interview met Herjan Coelingh Bennink, Olav Andriesse en Nathalie Bries in BiotechNEWS & Life Sciences

Pantarhei Bioscience: Eigen. Gedurfd. En uiteindelijk uitermate succesvol.

Pantarhei heeft in haar 23-jarig bestaan mooie stappen gezet. Maar bovenal draait medicijnontwikkeling om geduld en geld. Van allebei liefst veel. Prof. dr. Herjan Coelingh Bennink kan erover mee praten. Maar zijn team en hij geloven onvoorwaardelijk in de toepassingen van Estetrol (E4), ARC (Androgen Restored Contraception) en Zona Pellucida 3 Cancer (ZP3C).

Lees hier het interview met Herjan Coelingh Bennink, Olav Andriesse en Nathalie Bries in BiotechNEWS & Life Sciences.

 

 

Progesterone from ovulatory menstrual cycles is an important cause of breast cancer

On May 30, 2023 the leading scientific journal dealing with basic and clinical breast cancer research “Breast Cancer Research (BCR)” published the Perspective Review paper  “Progesterone from ovulatory menstrual cycles is an important cause of breast cancer” by Herjan J.T. Coelingh Bennink, Iman J. Schultz, Marcus Schmidt, V. Craig Jordan, Paula Briggs, Jan F.M. Egberts, Kristina Gemzell-Danielsson, Ludwig Kiesel, Kirsten Kluivers, Jan Krijgh, Tommaso Simoncini, Frank Z. Stanczyk and Robert D. Langer.

The most important message of this narrative review paper is that progesterone from normal menstrual cycles causes most BCs, whereas estrogens and androgens may stimulate existing hormone receptor positive BC, but do not cause BC. Four authors of this paper are related to Pantarhei (HCB, IJS, JFME and JK) and the other nine authors are experts in the field of Reproductive Endocrinology and Oncology, supporting this rather thought-provoking paper, that will hopefully lead to a reappraisal and a turnaround of the medical view and opinion on the cause of breast cancer and change the negative perception of estrogens.

Abstract: Many factors, including reproductive hormones, have been linked to a woman’s risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumours tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman’s lifetime risk of developing BC, and that breast tumours arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.

 

Annual Meeting of the American Association for Cancer Research (AACR), April 14-19, 2023, Orlando, Florida (US)

Our Director R&D, Iman Schultz, PhD, will attend the 2023 Annual Meeting of the American Association for Cancer Research held in Orlando, Florida (US), April 14-19, and present data on the discovery of the novel promising immunotherapy target ‘ZP3-Cancer’. ZP3-Cancer is highly selectively enriched in cancer, particularly in lung, colorectal, ovarian and prostate cancer.

The AACR Annual Meeting covers the latest breakthroughs in cancer, from early discoveries to late stage clinical trials, and attracts top speakers in the field from all over the world.

Looking forward to presenting our data in Orlando.

AACR-annual-meeting-2023

 

 

Treatment of serious COVID-19 infection by combining suppression of testosterone and using a high dose of estrogens

Pantarhei Oncology announces the publication of its scientific paper “Testosterone suppression combined with high-dose estrogen as potential treatment of serious COVID-19 infection” (Heliyon 8 (2022) e12376)

COVID-19 infections are more serious and have a higher mortality in males compared to females especially at ages above 50 years. This is related to the 10-20x higher testosterone (T) levels in males. Suppression of T in males with serious COVID-19 has no consistent effect on the clinical outcome. However, by suppressing T in males, also their estrogen levels are decreased while estrogens have a favorable inhibitory effect on the factors responsible for the COVID-19 infection. Therefore, we hypothesize that a combination of T suppression by androgen-deprivation therapy (ADT) and high-dose estrogen (HDE) treatment may be an effective treatment of serious COVID-19, to be confirmed in in seriously ill COVID-19 patients.

The scientific background of this hypothesis

Most studies report a higher incidence of serious COVID-19 infections in males compared to females especially at ages above 50 years, which may be due to sex-related immunomodulation. A resulting higher mortality rate has been published in Maturitas, both in a meta-analysis performed in May 2020 and in a recent retrospective analysis. These observations could be associated with the 10-20x higher testosterone level in males, since testosterone has unfavourable effects on the immune system, and also stimulates angiotensin converting enzyme-2 (ACE2) and the androgen-regulated protease transmembrane protease serine 2 (TMPRSS2), which both facilitate the entry of the COVID-19 virus into the cell. Testosterone suppression by ADT decreases the effects of ACE2 and TMPRSS2. Estrogen treatment (ET) has the same beneficial suppressive effect on ACE2 and TMPRSS2 as ADT. Both ADT and ET (ADET) have been investigated separately as possible treatments of SARS-CoV-2. We hypothesize that the ADET combination may be more effective than its components alone, as also suggested in our Research Letter in European Urology (2021), entitled ‘Treatment of Serious COVID-19 with Testosterone Suppression and High-dose Estrogen (HDE) Therapy‘. The ADET co-treatment has been investigated successfully by Pantarhei Oncology in patients with advanced prostate cancer (Eur Urol Open Science, 2021 & 2022). We searched the literature for evidence of COVID-19 treatment benefits with estrogens, progesterone, androgen deprivation, and anti-androgens. Data supporting the effect of ADT on SARS-CoV-2 are sparse, but the favorable effects of estrogens in relation to COVID-19 have been shown in various cohort studies.

Based on the outcome of our review and the mode of action of the ADET combination, we hypothesize that a combination of ADT and HDE may be an effective and safe treatment of serious SARS-CoV-2 and we propose to test this ADET hypothesis in a clinical trial.

 

“Maintaining bone health by estrogen therapy in patients with advanced prostate cancer: a narrative review”

Pantarhei Oncology proudly announces that its paper “Maintaining bone health by estrogen therapy in patients with advanced prostate cancer: a narrative review” “Maintaining bone health by estrogen therapy in patients with advanced prostate cancer: a narrative review” has been published in the journal Endocrine Connections after comprehensive review. This journal is an international peer-reviewed, scientific, open access journal in the field of endocrinology.

In this paper we review the new and safer estrogen therapies, including high dose estetrol (HDE4), to maintain bone mass and prevent fractures in advanced prostate cancer patients treated with androgen deprivation therapy (ADT).

 

Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study

Pantarhei Oncology proudly announces that its paper ‘Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study’ has been published in the journal European Urology Open Science after comprehensive review. This journal is an international peer-reviewed, scientific, open access journal in the field of urology.

This paper summarises the very important data on the beneficial effects of high dose estetrol (HDE4) on the Quality of Life of prostate cancer patients treated with androgen deprivation therapy (ADT).

 

European Urology Today, the official newsletter of the European Association of Urology, publishes the results of the PCombi study

European Urology Today, the official newsletter of the European Association of Urology, publishes the results of the PCombi study

Pantarhei Oncology has developed a new concept for the endocrine treatment of locally infiltrating and/or metastatic prostate cancer in collaboration with two renowned Dutch urologists, Prof. Frans Debruyne, formerly at the Radboud UMC, Nijmegen and Prof. Jeroen van Moorselaar, Free University, Amsterdam. This collaboration has resulted in the performance of the prospective, randomized, double-blind, placebo-controlled PCombi study in four Dutch urology centers by Dr. Erik Roos (Sneek), Dr. Rik Somford (Nijmegen), Dr. Ton Roeleveld (Alkmaar) and Dr. Tjard de Haan (Zwolle) in men with advanced prostate cancer, who started androgen deprivation therapy (ADT) with a luteinizing hormone-releasing hormone (LHRH) agonist to suppress testosterone levels. Major side effects of ADT are loss of libido and sexual function, but since the loss of testosterone also implies the loss of testosterone derived estrogens, especially estradiol (E2), most side effects of ADT are related to estrogen deficiency. These side effects are the same as the symptoms of estrogen deficiency occurring in postmenopausal women and include hot flushes and sweatings, joint pain (arthralgia), sleep disturbances, mood changes and depression, fatigue, loss of energy, muscle weakness (sarcopenia), cognition problems, bone loss and an increased fracture risk with, especially in aging males, a higher risk of mortality.

The results of the Phase II PCombi study were recently published in the European Urology Open Science.  The study has demonstrated several significant estrogen supplmentation and biochemical anti-tumor effects. Patients treated with E4 had fewer symptoms of estrogen deficiency than patients treated with placebo. The high dose E4 treatment was well-tolerated with no treatment-related cardiovascular adverse events.

European Urology Today, the official newsletter of the European Association of Urology, now reports on this publication: European Urology Today Vol. 33 No.5 – October 2021/ January 2022 by European Association of Urology (EAU) – Issue.

 

19th Association of Academic European Urologists Meeting (AAEU), December 2-5, 2021, Marseille (France)

19th Association of Academic European Urologists Meeting (AAEU), December 2-5, 2021, Marseille (France)

On 5th of December 2021, Prof. Jeroen van Moorselaar of the Amsterdam University Medical Centre in the Netherlands, lectured during the annual meeting of the AAEU in Marseille on the results of the PCombi study sponsored by Pantarhei Oncology. The title of his lecture: Estetrol improves quality of life in advanced castration-sensitive prostate cancer: a randomized clinical trial.

According to Prof. Van Moorselaar, the results were well received. He got a lot of enthusiastic reactions from the audience. He will give the same presentation at the International Prostate Cancer Update (IPCU) in Utah (US) beginning of March 2022.

 

 

Pantarhei Oncology receives positive advice from the FDA to initiate Phase III development of estetrol for prostate cancer treatment

Pantarhei Oncology receives positive advice from the FDA to initiate Phase III development of estetrol for prostate cancer treatment

After having achieved proof-of-concept in human for estetrol (E4) as a potential combination treatment with androgen deprivation therapy (ADT) of advanced prostate cancer, Pantarhei submitted a Pre-Investigational New Drug Application (Pre-IND) to the US Food & Drug Administration (FDA) for guidance on the further development with this new combination treatment.

In a positive meeting with the FDA, the company has reached an agreement on their development plans including a proposal for a Phase III clinical study. Based on this outcome, the PCombi project (E4 for prostate cancer patients) is now ready to start Phase III, the final stage of development to bring the product to the market.

The next study will be a pivotal phase III, randomized, double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of estetrol as co-treatment with ADT in patients with advanced prostate cancer. Main objectives are to evaluate E4 treatment for the prevention of estrogen deficiency symptoms caused by the ADT (such as hot flushes and bone loss) and for its additional anti-tumor effects.

The company is currently looking for a strategical or financial partner for further financing the development of this project.

 

 

Interview met Herjan Coelingh Bennink en Iman Schultz in BiotechNEWS & Life Sciences

Estetrol voldoet aan hooggespannen verwachtingen.

Goedkeuring voor het gebruik van het unieke natuurlijke zwangerschapsoestrogeen estetrol (E4) in een anticonceptiepil. Canada was recent de eerste, EMA en FDA volgden. Het zijn mijlpalen in het bestaan van Pantarhei Bioscience die het oestrogeen ontwikkelde. Maar het E4 toepassingsgebied is veel breder: binnen Pantarhei Oncology wordt het nu ook ingezet bij de behandeling van gevorderde borst- en prostaatkanker. Het ‘brein’ achter E4, gynaecoloog en reproductief endocrinoloog em. Prof. Dr. Herjan J.T. Coelingh Bennink (President en Founder) en Dr. Iman Schultz, Director R&D, vertellen.

Lees hier het interview met Herjan Coelingh Bennink en Iman Schultz in BiotechNEWS & Life Sciences.