|MGNX was not putting up any of the development costs after IND, so all they lose is the revenue stream. It is good to see they have enough irons in the fire that they don't feel compelled to continue development on their own. I have been watching MGNX recent share price recovery with some bemusement; apparently there was some investor optimism after the KITE buyout along the lines of "validates the CD-19 space." It looks poised to give back a chunk of that, and to my mind becomes more interesting. I had sold no September puts after my August puts expired worthless and MGNX tacked on 20% in a week or two for no apparent reason (other than being oversold).|
We both would like to see focus on programs where they are closer to the front of the pack on the race.
ESMO abstracts now => MGD006 data:
>>995O - Interim results from a phase 1 first-in-human study of flotetuzumab, a CD123 x CD3 bispecific DART molecule, in AML/MDS
Acute myeloid leukemia (AML) CD34+, CD38- cells highly express CD123, associated with high-risk disease and disease progression. CD123 expression on normal HSC is negligible, enabling a promising strategy of preferential ablation with a CD123-targeted approach. Flotetuzumab (MGD006/S80880), a novel CD123 x CD3 bispecific DART protein, is designed to target CD123+ cells for elimination by T cells.
The Ph 1 dose-escalation study will define the safety profile, maximum tolerated dose and schedule (MTDS), and preliminary anti-leukemic activity of flotetuzumab. Relapsed/refractory (R/R) AML or intermediate-2/high-risk MDS will be treated with 28?day cycles of continuous infusion at doses from 3 to 1000?ng/kg/day. During C1W1, patients receive a lead-in dose (LID) of 30?ng/kg/day for 3 days followed by 100?ng/kg/day for 4 days. During C1W2-4, patients receive the cohort target dose (300-1000ng/kg/day) on either a 4-day on/3-day off or a continuous 7-day on weekly schedule. At Cycle 2 and beyond, patients are treated on a 4-day on/3-day off schedule at the cohort target dose for a maximum of 12 cycles, 2 cycles after a CR, DLT or DP. Cohort expansion will enroll 24 AML and 24 MDS patients at the MTDS. Disease status is assessed by IWG criteria.
Patients with R/R AML/MDS (35/3) have been treated with flotetuzumab, up to a dose of 500ng/kg/day. Flotetuzumab has demonstrated acceptable tolerability to date, with no MTDS yet defined for either schedule. The most common drug-related adverse event was infusion-related reaction/cytokine-release syndrome (29/38, 76% any grade; 3/38, 8% G3). Drug-related adverse events =G3 were observed in 14/38 (36%) of patients overall. A LID strategy and early use of tocilizumab ameliorated this toxicity and limits corticosteroid use. At 500ng/kg/day, anti-leukemic activity has been observed in 4/8 patients treated, including CRi (n?=?2), morphologic leukemia free state (n?=?1) and bone marrow blast reduction >50% (n?=?1).<<
Looks like OK efficacy, but that 36% G3+ tox is an issue. If only 3 G3+ patients are CRS, what are the other 11? And they don't even mention CRis at doses lower than 500ng, which is probably where most of the G3s come from. This is "acceptable?"