An unofficial update on Decibel Therapeutics’ secretive gene therapy program to treat sensorineural hearing loss by regenerating cochlear outer hair cells…
First, the official story, followed by a big “unofficial” update on “DB-301″…
Laurence Reid, CEO of Decibel Therapeutics, had this to say during a recent presentation at the 20th Annual Needham Virtual Healthcare Conference – from April 15, 2021:
Laurence Reid: We have an earlier stage program with respect to the cochlea. The goal is to drive differentiation of the supporting cell, through an immature hair cell, and then on particularly to either generate the outer hair cell or potentially the inner hair cell – for treating different types of patient populations with different cellular bases for their hearing loss.
Here is a slide from the presentation:
Officially, we also have some background information thanks to a recent Decibel Therapeutics, Inc SEC filing (emphasis ours):
Cochlear Hair Cell Regeneration
Age-related hearing loss and noise-induced hearing loss affect millions of people in the United States and Europe. Research has shown that the degree of hearing loss in these populations is best predicted by the amount of outer hair cell loss. We believe that restoring outer hair cells could restore hearing in these individuals. In our cochlear hair cell regeneration program, we are designing an AAV-based gene therapy that utilizes cell-selective expression of reprogramming factors to convert supporting cells into outer hair cells. We are currently conducting preclinical in vitro and in vivo rodent studies to evaluate the cell-selectivity of certain proprietary promoters and the ability of certain reprogramming factors that may drive an outer hair cell fate.
In that same filing, we learn that Decibel Therapeutics plans to announce the targets for this cochlear hair cell regeneration program in 2022. Excerpt and pipeline snapshot:
In addition, we are advancing our cochlear hair cell regeneration program to treat acquired hearing loss by regenerating cochlear outer hair cells. We plan to announce the targets for our cochlear hair cell regeneration program in 2022.
However, we might not need to wait until 2022 for that update, because…
Our independent research has uncovered what appear to be details related to Decibel’s “Cochlear Hair Cell Regeneration Program” (a.k.a. the gene therapy program which could potentially be given the name “DB-301”)…
That’s our unofficial code name, inferred from Decibel’s naming scheme (“AAV.RF301” or “AAV.301” + “DB” = DB-301).
From a Decibel Therapeutics corporate overview presented during Citi’s 15th Annual BioPharma Virtual Conference:
As you can see, this slide looks like a perfect match for the cochlear hair cell regeneration program. (Which is why we’re calling this an “early update” on the program.)
The presentation has the word “confidential” written on page 19.
However, the source of this information – a PDF document – is currently available on Decibel’s website. (It is indexed by search engines and accessible to the public. We have archived it digitally as well, for record-keeping purposes.)
Furthermore, within this PDF – on page 19, in very, very, very tiny text – is a list of what appear to be outer hair cell candidate targets (copy+pasted):
Hdac3 Kdm4a Mtpn Htatip2 Dnmt3a Mlxip Foxo3
oxn3 Prnp Sall1 Pknox2 Klf9 Rora Six2 Trps1 Actn4 Mef2a Pdcd11 Nfkb1 Hlcs Zfp410 Banp Zbtb7b Esrra E2f3 Zfp740 Zkscan3 Creb3l1 Ighm Zfp324 Arnt Lig1 Elk3 Zbtb40 Crem Smarca2 Nfatc2 Rest Nfib Zfp608 Nfix Smad7 Mafk Adarb1 Irf6 Nacc2 Rorb Bhlhe40 Ikzf2 Jun Zfp423 Nr3c1 Tppp Cat Zfp637 Zfp777 Kmt2a Nr2f2 Zfp592 Pura Zfp365 Zbtb46 Zfp654 BC005561 Zfp516 Cic Zhx3 Rxra Zfp106 Zfp277 Thra Tmem33 Zc3h7a Srrm3 Pds5a Zbtb4 Ube2k Ctbp2 Id4 Srebf1 Nfat5 Ddit3 Sall3 Mdm2 Srebf2 Gtf2i Prdx5 Smap2 Zbtb7a Zfp618 Gata3 Irf9 Mef2d Taf1 Zfp523 Kdm2a Abcf2 Zfp398 Zfp638 Hmg20a Msi2 Nmral1 Tead1 ead2 H2afy Irx3 Ezh2 Rfxap Sox9 Tgif2 Egr4 Egr3 Npas4 Sox11 Fhl2 Prox1 Sox2 Cers2 Gm10093 Dazap1 Dnajc21 Isl1 Ran Ebf1 Atoh1 Hes6 Rpl35 Rps10 Psma6 Akr1a1 Barhl1 Smarca5 Ruvbl1 U2af1 Gtf2a2 Zfp428 Ssbp3 Zfp326 Nuak1 Pknox1 Cyb5r1 Tceal5 Msra Cers6 Zmat4 Bcl11b Npdc1 Bcl2 Ybx1 Stub1 Zmat2 Zfp667 Yeats4 Tfdp2 Hnrnpa1 Tfdp1 Rbm17 Hmgn3 Lhx3 Cers4 Ugp2 Bax Mrps25 H1fx Nap1l1 Pax2 Traf4 Mcm6 Neurod6 Rab2a Cd59a Ptcd1 Klf7 Las1l Cdk2ap1 Mycl Nono Zfp330 Insm1 Irx2 Id1 Id2 Magoh Nr2f6 Zbtb20 Diablo Gar1 Snrpb2 Rps4x Zmiz1 Hnrnpc Nr2f1 Rbpj Lsm6 Hmgb2 Tbpl1
Is this a short list of targets that Decibel is planning to choose from and announce in 2022?
Time will tell.
But, taken together, all this information leads us to believe that Decibel Therapeutics could have an earlier update for us about all these “unofficial” details (including the name “DB-301”, which is just one possibility).
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