Thread by @mchilberg

SM presenting yesterday at HC Wainwright made a couple references to #Fabry study which prompted this thead
- No steroids have been used.
- Best data he's had the privilege to report
investor.sangamo.com/events/event-d…
$SGMO
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Fabry disease = abnormal a-Gal enzyme activity leading to Gb-3 and lyso-GB3 accumulation. Prevalence data varies widely given multiple attempts to quantify the impact of under-diagnosis. Kidney and cardiac disease are LT impacts
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ERT is the SOC for patients with #Fabry. The LT follow up studies for patients on ERT show that it does not stop disease progression and imposes a high treatment burden.
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$SNY #Replagal LT follow up study showed 42/52 patients experienced no severe clinical events during period. However, 10 patients reported a total of 16 events: 4 had severe kidney event, 2 patients had cardiac events including one death.
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ERT for #Fabry helps many but there remains a high treatment burden and an unmet need for a significant portion of the patient population. Kidney and cardiac disease continues as an outcome for patients.
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The genomic medicine sector is attempting to address this unmet need but the field has been reduced. $AVRO terminated their autologous cell therapy program. $FOLD terminated their program which was to be included in a failed SPAC rollout. $SGMO and $FDMT are in the clinic
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$FDMT has dosed 3 patients who all had history with ERT. One had aHUS SAE which led to a protocol amendment and caused company to consider moving to a lower dose for cohort 2. No updates are expected until 1Q23
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$SGMO ST-920 has completed dose finding studies and is now in cohort expansion. Yesterday SM stated that they decided to eliminate steroid preconditioning due to the pandemic and none has been needed after treatment.
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$SGMO study appears exceptionally well designed. They have a mix of on-ERT, off-ERT and ERT-naive patients enrolled with early data indicating a clear enzyme expression relationship between these profiles. Focus on eGFR cMRI LVM included in secondary endpoints
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A recap of the $SGMO study readouts is attached. Later this year we should get some substantive data on cohort 3-4 given these patients were dosed between 24-46 wks ago.
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One focus point worth watching is the data on kidney/cardiac disease biomarkers eGFR and cMRI LVM. $SGMO has a Kidney cohort (3d) and Cardiac cohort (3e). Baseline info on eGFR has included for the first 2 patients who both show early stage kidney disease.
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$FDMT next steps are unclear given protocol amendment and discussion of dose reduction. They also did not include any patients with early stage kidney disease (see eGFR >100) nor did they dose any patients that were ERT naive making it challenging to assess the next readout.
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Bottom line: $SGMO preliminary data appears very strong and the clinical design has provided an exceptional foundation that appears to support the view that this is well-situated as a P3 trial candidate.
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$SGMO has minimized the possibility of accel approval. $VRTX discussion recently on VX147 for APOL-1 is worth a listen. eGFR slope usually takes more than 6-12 months to show so proteinuria measurements may be introduced.
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