The following is excerpted from the question-and-answer section of the transcript.
(Questions from industry analysts are provided in full, but answers are omitted - download the transcript to see the full question-and-answer session)
Question: Nalin Tejavibulya - Jefferies - Analyst
: Got it. Thank you very much, Julian. So with the data from Cohorts 1 and CF showing that about 40% of the epithelial cells expressing transgene
RNA, and then more than 92% of the cells being positive for CFTR, could you please discuss how we should be thinking about the data in terms of
transduction expression and clinical improvement in the higher-dose cohorts that you're expecting to show in November?
Question: Nalin Tejavibulya - Jefferies - Analyst
: Got it. In terms of combination therapy, I think previously you've expressed that there could be synergy. Could you please talk a little bit about
what kind of synergy you're expecting in addition to having CFTR modulator thinning out the mucus to improve transduction, but you're already
seeing 92% to 99% of the cells being positive. So what further synergy could we potentially expect across the different CF mutations?
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JUNE 09, 2023 / 2:00PM, FDMT.OQ - 4D Molecular Therapeutics Inc at Jefferies Healthcare Conference
Question: Nalin Tejavibulya - Jefferies - Analyst
: So the data is early, but maybe could you discuss how you're thinking about what kind of PPFEV1 shown here for the three patients would mean
for those who are eligible for CFTR modulators? And what kind of improvement we could realistically achieve with combination therapy? Is there
any form of upper bound of FEV1 improvement that one could achieve?
Question: Nalin Tejavibulya - Jefferies - Analyst
: Got it. And with 4D planning to meet with the regulator in the fourth quarter to discuss pivotal trial plans, could you please give us a little bit of
color on what the trial might look like and what the timeline might look like for pivotal trial initiation, number of patients, and primary endpoints?
Question: Nalin Tejavibulya - Jefferies - Analyst
: Got it. And in terms of durability of this therapy, obviously there hasn't been an inhaled gene therapy that's been this successful before. You've
seen evidence of transduction of long-lived basal cells and, amongst many other cells, goblet cells and lamina cells. So could you please help us
understand what this may imply in terms of treatment durability? How long before you might lose clinical efficacy?
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JUNE 09, 2023 / 2:00PM, FDMT.OQ - 4D Molecular Therapeutics Inc at Jefferies Healthcare Conference
Question: Nalin Tejavibulya - Jefferies - Analyst
: All right. So with this capsid having shown the potential to achieve widespread transduction in lung cells, obviously there are additional applications
for this capsid. Could you please discuss what the data and CF shown here would suggest in terms of the performance of the A101 capsid and
additional indications, for example, in AATD, which is a completely different kind of disease where you have secretion impairment?
Question: Nalin Tejavibulya - Jefferies - Analyst
: Understood, and I want to touch on the ophthalmology franchise a little bit. So you showed some efficacy data in wet AMD previously, and then
for DME, Phase 2 will begin imminently, starting at a lower dose compared to wet AMD. Could you please talk us through the different dose levels
selected for the two populations? Is it kind of for safety concerns, since DME patients are younger and may be more prone to inflammation compared
to wet AMD, or is it a matter of efficacy?
Question: Nalin Tejavibulya - Jefferies - Analyst
: Got it, and then based on literature and from our discussions with KOLs, the response rate in DME appears to be a little lower than in wet AMD,
and some patients would even need to have intravitreal steroid and/or control glucose levels in order to achieve good response in anti-VEGF. I was
wondering if you've had any feedback from investigators involved in the PRISM trial in terms of concern for 4D-150, how it would work in DME.
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JUNE 09, 2023 / 2:00PM, FDMT.OQ - 4D Molecular Therapeutics Inc at Jefferies Healthcare Conference
Question: Nalin Tejavibulya - Jefferies - Analyst
: Understood. And then for additional indication in geographic atrophy, maybe -- I was wondering if you could please give an update and then
compare and contrast in terms of complement factor H inhibition that you're using compared to what competitors are using with complement
factor I inhibition.
Question: Nalin Tejavibulya - Jefferies - Analyst
: And lastly, for the Fabry disease program, should the clinical hold be successfully removed? Could you please help us understand how you're
planning to proceed towards the pivotal trial in cardiomyopathy? What would you need to see in order to be confident that the program would
succeed in a pivotal trial?
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