- Here are my notes from the Myrexis $MYRX (formerly Myriad Pharma. Click here for my complete research notes page) webcast at the Jefferies conference on 6/6/11:
- Company is only interested in potentially best in class compounds
- Company wants early POC- all p2 trials will be comparative arm trials (ie, no open label trials)
- Azixa is a tubulin disrupting agent - same class as taxol, vincristine (aka Oncovin) and vimblastine (aka Velbe), but is differentiated because (unlike the above 3 drugs) it is not a substrate for multiple drug resistance (MDR) pumps and therefore freely crosses the blood brain barrier (aka BBB, which primary consists of said MDR pumps)
- Azixa accumulates in neuronal tissue- hardly any is found in CSF. Over 160 pts treated so far and seen no indcation of any neurotoxicity (cognitive or motor function). Drug appears to be benign to normal non-dividing neural cells - only kills dividing cancer cells
- Melanoma pts with brain metastases are generally exlcuded from most melanoma trials - because it is assumed/known that the drugs being tested do not cross the BBB
- Results to date suggested improved PFS and OS compared to temozolomide alone, no indication of additive toxicity.
- carboplatin combo in GBM- saw activity, no additive tox (but lots of tox for carboplatin itself)
- RECIST criteria is more appropriate for peripheral disease, had used McDonald criteria for progression in completed azixa studies
- showed pics from pt that is now disease free but only stayed on drug due to breach of protocol- but informed design of p2b trial - using RANO criteria now, see below
- 2nd line temo failure single agent (avastin experienced or naive)-life expectancy after avastin failure is in weeks. 1 pts had ~1 yr with 80% reduction in tumor.
- p2b combo ongoing in 1st line GBM. change progrsssion from mcdonald to RANO criteria (published NEJM 2010)- keep pt in trial for one further cycle after appearance of possible progression.
- doing dose escalation w/ radiation- preliminary data suggest no added tox. hope to progress rapidly into comparative portion (so note that Azixa is actually not yet in a randomized p2b portion of the trial)
- MPC3100 oral HSP90 inhibitor- no liver tox, able to prodrug as MPC-0767- much more soluble, easier to formulate. only MPC-3100 product is ever absorbed into pt.
- Work by myrx and others is showing that hsp90 benefit appears to be in preventing resistance to targeted inhibitors (such as ALK in lung, bRAF in melanoma)
- oral hsp90 inhibitor advantage- combo w/ other oral cancer drugs. also can dose daily to maintain constant blood concentration- appears to be most effective.
- plan to move prodrug forward using bioequivalnce studies not full toxicology (has not been okayed by fda though)
- I don't believe he mentioned a timeline for p1 MPC-3100 data...disappointing
- cancer metabolism inhibitors- IND development stage for lead MPC-9528 and prodrug MPC-8640 (don't remember this being mentioned on prior webcasts, but may have been on one of the AACR posters this April 2011) compounds
- significant synergy w/ DNA damaging agents like 5-FU, temozolomide, and PARP inhibtiors- points towards CRC as first indication (new comment)
- oral IKK-epsilon inhibtiors- don't know of anyone else w/ medicinal chemistry program against this target
- have 2 published patents
- IKKe- part of innate immunity pathway. Drug is selective, no effect on TNF-alpha pathway
- RA study done at CRO (data reported at EULAR 5/2011), but company is more interested in lupus. Unfortuantely takes 1 yr to develop lupus mouse model- sounds like maybe they are working on this in house now.
- no q&a on webcast - had breakout session