Conference Reports
237th ACS Spring Meeting
Salt Palace Convention Center, Salt Lake City, Utah, USA, 22-26th March 2009
In the shadow of the towering peaks of the Wasatch Mountains, Salt Lake City brought together a vast number of delegates from all areas of chemical research for the 237th ACS meeting and exposition. In the grand expanse of the Salt Palace Convention Center, experts gathered together to discuss individual research, collaborations and showcase new findings and data. Also in attendance were names from the pharmaceutical industry, from small to mid-sized companies, right up to the giants of Big Pharma. The mix of commercial and academic interest made for a diverse environment, truly appealing to all areas of chemical and medical research.
The opening day of the conference included the eagerlyawaited
first disclosure session. First onto the stage was Bristol-
Myers Squibb, which presented data on their gamma secretase
inhibitor, BMS-708163, for the treatment of Alzheimer's
disease (AD). Recent preclinical data has shown
BMS-708163 to dose-dependently reduce levels of Aß40 in
rats and dogs, while producing no notch-related gastrointestinal
or lymphoid effects. It is currently in a Phase II trial in
Europe and the US in 200 AD patients to evaluate the safety,
efficacy and pharmacokinetics of once-daily oral doses of 25-
125mg. With a significant unmet medical need for AD drugs,
BMS-708163 may yet provide a much-needed treatment option
for this disease.
Also attracting attention was Amgen, which gave first-time data on its 11ß-hydroxysteroid dehydrogenase (HSD) inhibitor, AMG-221, for the treatment of metabolic disorders such as Type II diabetes. In in vivo data presented at the session, AMG-221 was reported to have low clearance, and oral doses were shown to reduce insulin and glucose levels in dietinduced obese mice. It has also been shown to inhibit adipose 11ß-HSD activity in humans after a single oral dose. The compound is currently in Phase I trials.
Presenting in the first disclosure session was Pfizer, with an interesting insight into the development of PF-2413873, a progesterone receptor antagonist for the treatment of endometriosis. Newly-disclosed preclinical data showed PF- 2413873 was potent and selective and blocked estradioldriven endometrial growth at the proliferation stage of the menstrual cycle. In a Phase I single-dose pharmacokinetic trial, PF-2413873 was well tolerated at oral doses up to 300mg, and showed a half-life suitable for once-daily dosing. A Phase I trial for endometriosis is ongoing. Endometriosis represents a significant unmet medical need, with Pharmaprojects' data indicating just 4 drugs in the clinic for this condition, with Repros Therapeutics' Proellex currently negotiating the clinical tightrope of Phase III trials. Of those in clinical trials, gonadotropin-releasing hormone receptor antagonists currently dominate the field. Only time will tell if the early clinical promise of PF-2413873 can net Pfizer a place among this market.
Concluding a flurry of first disclosures from Big Pharma was an informative presentation by Merck, outlining the discovery and ongoing development of its androgen receptor modulator, MK-0773. This compound is under development for the treatment of sarcopenia. In a randomized, double-blind, placebocontrolled Phase IIb trial in 67 postmenopausal women, MK-0773 increased lean body mass and markers of bone anabolism, with no increases in sebum excretion rate or sebaceous gland volume. A Phase II trial to evaluate safety and efficacy of twice-daily 50mg doses of MK-0773 is underway, with completion expected in June.
Also raising interest in the oral sessions was Bristol-Myers Squibb's IGF-1 inhibitor, BMS-754807, under development for the treatment of breast cancer. The compound has shown potency both in vitro and in vivo, and is active in human xenograft models of IGF-1 driven tumours. It also shows synergism in combination with cetuximab. Clinical studies are underway, including a Phase II trial in 48 advanced HER2+ breast cancer patients to evaluate safety, tolerability and pharmacokinetics of daily administration. Pharmaprojects' data indicates no currently- launched IGF-1 inhibitors for cancer indications, with the most advanced being Pfizer's figitumumab, currently in Phase III trials for non-small cell lung cancer.
Poster sessions once again featured prominently in this year's programme, with interesting presentations from both the worlds of pharmaceutical and academic research. Santhera Pharmaceuticals presented data on its preclinical MC-4 receptor antagonist programme, for the treatment of cancer cachexia. Preclinical studies showed lead candidate SNT- 20707 to have 'excellent' selectivity towards both MC3 and MC4 receptors. In a mouse cachexia model, it was protective and stimulated food intake. Clinical trials are planned for 2010.
Australian pharmaceutical company Cytopia presented data on its tubulin inhibitor, CYT-997 for the treatment of cancer. The compound has shown vascular disrupting activity below maximum tolerated dose in preclinical studies, and potent antitumour efficacy in xenograft models. CYT-997 is in Phase II trials for multiple myeloma, as well as Phase I/II trials for breast and prostate cancer.
Also attracting attention in the poster sessions was Organon (Schering-Plough), presenting data on its FSH receptor agonist Org-49035-0 for the treatment of female infertility. This compound targets an allosteric site on the FSH receptor. In a rat superovulation model, doses of Org-49035-0 2-4mg/kg increased ovarian weight and number of ova.
Another early-stage compound presented at the poster sessions was Kyorin's neutrophil elastase inhibitor, AX-9657. Currently under development for lung diseases including acute lung injury and cystic fibrosis, AX-9657 was potent and selective, and inhibited HNE-induced lung haemorrhage in preclinical studies. It distributes effectively in the lung following iv administration. Clinical studies are planned.
Carrying on the success of previous meetings, the 237th American Chemical Society conference once again offered an exciting array of revelations from the pharmaceutical industry and the prospects for yet another successful and informative meeting next year are just as high.
Jonathan Stephens
Editorial Analyst
Photograph courtesy of Skyguy414
