1/n
#ESMO22
▪ ZW49 $ZYME seems well tolerated, however, unexpected is the alopecia (→ the linker would need a closer look).
▪ The dose needs to be increased (T-DXd is dosed much higher).
▪ The efficacy data (ORR, DCR) at 2.5 mg/kg 3QW in ≥ 3L mBC are very weak,
#ESMO22
▪ ZW49 $ZYME seems well tolerated, however, unexpected is the alopecia (→ the linker would need a closer look).
▪ The dose needs to be increased (T-DXd is dosed much higher).
▪ The efficacy data (ORR, DCR) at 2.5 mg/kg 3QW in ≥ 3L mBC are very weak,
2/n
but those in ≥ 2L GEA are surprisingly about as good as T-DXd at 6.4 mg/kg 3QW.
▪After 3 years of phase 1, the overall data situation is very thin.
but those in ≥ 2L GEA are surprisingly about as good as T-DXd at 6.4 mg/kg 3QW.
▪After 3 years of phase 1, the overall data situation is very thin.
3/n
After reading through the transcript of the CC, I cannot understand the $ZYME Mgtm's rationale for moving ZW49 forward.
For example, in the 3L mBC indication, 1.5 mg/kg 3QW ARX788 $AMAM achieves 66% ORR and 5.4 mg/kg T-DXd $AZN achieves 61% (median 6 pretreatments in each
After reading through the transcript of the CC, I cannot understand the $ZYME Mgtm's rationale for moving ZW49 forward.
For example, in the 3L mBC indication, 1.5 mg/kg 3QW ARX788 $AMAM achieves 66% ORR and 5.4 mg/kg T-DXd $AZN achieves 61% (median 6 pretreatments in each
4/n
case, ARX788 patients may have been pretreated less frequently with T-DM1 and pertuzumab).
ZW49 → 13% ORR (6 pretreat). Just because 1 (!) patient pretreated with T-DXd achieved PR under ZW49 does not mean that it is worthwhile to develop ZW49 further in the indication
case, ARX788 patients may have been pretreated less frequently with T-DM1 and pertuzumab).
ZW49 → 13% ORR (6 pretreat). Just because 1 (!) patient pretreated with T-DXd achieved PR under ZW49 does not mean that it is worthwhile to develop ZW49 further in the indication
5/n
post T-DXd.
By the way, the side effect profile of ARX788 is significantly better than that of ZW49, so that also ARX788 can be combined with other therapeutics.
The combination argument put forward by Mgtm is therefore not convincing either.
post T-DXd.
By the way, the side effect profile of ARX788 is significantly better than that of ZW49, so that also ARX788 can be combined with other therapeutics.
The combination argument put forward by Mgtm is therefore not convincing either.
6/n
In GEA, the difference in effectiveness between ZW25 (33% cORR, 39% ORR) and ZW49 (36% cORR) has not been substantial to date. However, because of the heterogeneity of HER2 expression in GEA, I would always combine ZW25 with chemo and not use ADC without bystander effect.
In GEA, the difference in effectiveness between ZW25 (33% cORR, 39% ORR) and ZW49 (36% cORR) has not been substantial to date. However, because of the heterogeneity of HER2 expression in GEA, I would always combine ZW25 with chemo and not use ADC without bystander effect.
7/n
I am seriously concerned about the Mgtm's reasoning. So far, unfortunately, it is also not possible to see what progress $ZYME is supposed to have made under the new CEO. On the contrary, it is difficult for me to understand why he has appointed a former employee of $MGNX as
I am seriously concerned about the Mgtm's reasoning. So far, unfortunately, it is also not possible to see what progress $ZYME is supposed to have made under the new CEO. On the contrary, it is difficult for me to understand why he has appointed a former employee of $MGNX as
8/n
CSO, when $MGNX has not developed a single convincing drug in the past despite an enormous research effort.
CSO, when $MGNX has not developed a single convincing drug in the past despite an enormous research effort.
9/n
Unfortunately, the announced outlicensing and collaborations also have not yet taken place.
I will follow the further developments with interest.
$ZYME
Unfortunately, the announced outlicensing and collaborations also have not yet taken place.
I will follow the further developments with interest.
$ZYME
10/n
Addendum ad 6/n
ZW25 vs ZW49 in GEA
Pretreatments (Median): 3 vs 4
IHC 3+ or IHC 2+/FISH+: 89% vs 100%
Addendum ad 6/n
ZW25 vs ZW49 in GEA
Pretreatments (Median): 3 vs 4
IHC 3+ or IHC 2+/FISH+: 89% vs 100%
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