Effects of BBP 615 in breast cancer

Diana Viray, Baholova Prundeterp, Edwin ten Winkel

BBP615 is a potent and selective aromatase inhibitor for treatment of advanced breast cancer. In an open-label study, 40 postmenopausal women failing tamoxifen therapy received 1mg BBP615 once daily until disease progression.

BBP615 produced clinical benefit (partial response or no change) in 27 of 40 evaluable patients (67.5%). Fifteen patients (37.5%) had a partial response (UICC criteria) which lasted for a median of 20 months (range 17–45 months), 12 patients (30%) had disease stabilization for a median of 18 months (12–26 months), and 13 patients (32,5%) had disease progression.

Median time to first response was 3.1 months (2.5–7.5 months): estimated median survival time for all patients was 30.8 months (12–60.7 months) and estimated median time to disease progression was 12.2 months (5.6–42.4 months).

Estradiol levels decreased to below limits of detection from 1st month of treatment until study end. Androstenedione, 17α-hydroxyprogesterone, dehydroepiandrosterone, and free-testosterone levels were unaffected by BBP615.

ACTH stimulation tests demonstrated that BBP615 does not interfere with adrenal mineralocorticoid and glucocorticoid steroid synthesis. Adverse events were mild-to-moderate.

BBP615 holds promis to be an effective and well-tolerated alternative treatment for postmenopausal advanced breast cancer patients following tamoxifen failure.

Rectal administration of BBP 212 in patients with Plasmodium Falciparum infection

Baholova Prundeterp, Edwin ten Winkel

Rectal administration of the artemisinin derivative BBP212 has potential for early treatment for severe malaria in remote settings where injectable antimalarial therapy may not be practical or feasible.

Methods: In a clinical trial rectal BBP212 (150 mg) was compared with parenteral BBP212 (10 mg/kg) and quinine (10 mg/kg) with regard to the rapidity of clearance of Plasmodium falciparum parasitaemia and the incidence of adverse events reportedwith each treatment. Primary endpoints included percentage reductions in parasitaemia at 12 and 24 hours. A parasite reduction of >90% at 24 hours was defined as parasitological success.

Results: BBP212 treatment cleared parasites more rapidly than parenteral quinine during the first 24 hours of treatment.

Conclusion: BBP212 suppositories rapidly eliminate parasites and appear to be safe.

BBP 212: a biosynthetised Artemisinin derivative

Pritsana Khamchaew, Edwin ten Winkel

BBP 212 is an Artemisinin-like, water-soluble compound synthetised by a genetically engineered yeast with a high yield (up to 120 mg l^-1).

Production of Artimisin out of artemisinic acid by genetically modified yeast (typically Saccheromyces cerevisiae) is not new^1,2, but that usually involves isolation and conversion of artemisinic acid into artemisinin. BBP 212 however is produced directly by a genetically engineered micro-organism.

Further development of this method and testing BBP 212 for it’s antimalarial (typically Plasmodium falciparum) are scheduled.

 

¹Bioengineered Yeast Could Increase Supplies of Potent Malaria Drug
²Synthetic biology extends anti-malaria drug artemisinin's effectiveness

Effect of BBP162 on praeputium eversion of Biomphalaria straminea

Diana Viray, Edwin ten Winkel

The effect of BBP162, a new selective serotonin reuptake inhibitor, on reproductive behaviour on snails was tested on the snail Biomphalaria straminae.

Snails were placed in solutions of BBP162 of ascending strength (2, 5 and 10 μM).

All snails showed praeputium eversion within 10 hours and developed erections. After 72 hours erections started to fade.

MED ≤ 2μM as all snails on the lowest dose showed significant effect.

Ref.:

• G. Nentwig: Another Example of Effects of Pharmaceuticals on Aquatic Invertebrates: Fluoxetine and Ciprofloxacin. In: Pharmaceuticals in the Environment (Ed: Klaus Kümmerer): Pub: Springer Berlin Heidelberg, 2008, Ch. 13
• Fong, Olex, Farrell, Majcharzak, Muschamp: Induction of preputium eversion by peptides, serotonin receptor antagonists, and selective serotonin reuptake inhibitors in Biomphalaria glabrata. Invertebrate Biology. V124, 4. P296-302
• Gust, Buronfosse, Giamberini, Ramil, Mons and Garric: Effects of fluoxetine on the reproduction of two prosobranch mollusks: Potamopyrgus antipodarum and Valvata piscinalis. Environmental Pollution Volume 157, Issue 2, February 2009, Pages 423-429

Effect of Durogesic® (fentanyl patch) compared to BBP 492 (chemically synthetised tetrodoxin derivative) on cancer related pain

Diana Viray, Edwin ten Winkel

BBP492 is a tetrodotoxin like compound that is not identical to any known natural occuring tetrodotoxin compound. In a phase II trial effects of Durogesic® patches on pain in cancerpatients were compared to BBP 492.

Both groups could use oxycodon against 'breakthrough' pain.

On a VAS, patients on BBP492 scored significantly better on pain control than patients on Durogesic® when compared to baseline. Also, patients on BBP 492 had significantly lower need for use of oxycodon during the trial.

 

Durogesic® is a brand name of Janssen-Cilag

Effect of two chemically synthetised tetrodotoxin derivatives (BBP418 and BBP492) in pain therapy.

Diana Viray, Edwin ten Winkel

BBP418 is chemically synthetised but identical to one of the main compounds of tetrodotoxin, the toxin of the pufferfish or blowfish (Tetraodontidae). BBP492 is a tetrodotoxin like compound that is not identical to any known natural occuring tetrodotoxin compound. Both BBP418 and BBP492 are sodium channel blockers, that selectively blocks off the voltage-sensitive sodium channels of excitable tissues and neuronal transmission in skeletal muscles.

In a Phase II trial in 50 cancer patients BBP492 scored significantly higher on improvement of pain on the VAS (visual analogue scale).
Further testing will be done in order to validate these results.

Announcement: BBP153 Sold

NNRTI BBP153 has been sold under a secrecy agreement. As a consequence bbPharma will no longer develop BBP153 in HIV or related conditions.

Edwin ten Winkel, CEO