IK-930 (TEAD inhibitor) ✔️
Ikena Oncology
Note: Originally figured this one out on January 26, 2023 and posted on Twitter on February 6, 2023. Confirmed correct on March 6, 2023.
IK-930 is an oral transcriptional enhanced associate domain (TEAD) inhibitor developed by Ikena Oncology (IKNA 0.00%↑). It is currently being evaluated in phase 1 trials in advanced solid tumors with/without genetic mutations to the Hippo pathway (NCT05228015). TEADs are involved in cell proliferation, tissue homeostasis, and regeneration.
Detective work for this compound was done by request! Here’s a plug: if there’s a compound you might be interested in having me look at, subscribe & click the link at the bottom of this post for access to the suggestion link :)
Back to the TEAD inhibitor. I start with the patent space. Since Ikena is a smaller company, I was curious to know what their patent landscape looked like for this program. Turns out, there are 2 patents (as of February 6, 2023) on TEAD inhibitors:
Composition of matter: WO 2022/120353 A1
Combination therapy: WO 2022/159986 A1
Good things come in threes (or twos!)
Combo patents always catch my eye. This is because there’s usually loads of in vivo data with the compound of interest that serve as breadcrumbs to the meat of the matter. If a company has made the effort to patent a combination, the experimental compound is probably pretty far in the (pre)clinical development pipeline.
So immediately, I jump to the combo patent (‘986). What I find is extensive characterization of an experimental TEAD inhibitor “T-A-32” in cell-based and tumor xenograft models.
As the patent title would suggest, there’s also data on T-A-32 combined with an EGFR inhibitor and/or a MEK inhibitor.
The dollars are in the details
There’s a lot going on here. But there are 3 details I keep in mind, which could be big clues as I continue with my search:
General shape of the graphs (the apoptosis data, in particular, have a very distinct shape).
Upper and lower boundaries of the axes
Doses
Do not trust, only verify
The combo patent (‘986) provides a structure for T-A-32. But is this really the structure of IK-930? Or is it a decoy compound? I’ve seen decoy compounds in patents before (ahem, GS-5245) and therefore need to make sure that this is really IK-930!
I comb through the composition of matter patent (‘353). The structure corresponding to T-A-32 is not there. But the SAR is definitely heading in that direction. Huh. A bit concerning. There are some structures that appear to be redacted (?) in the COM patent.
Time to look beyond patents.
Luckily, I come across an SEC S-1 filing. I love SEC filings because the company cannot lie.
In the SEC filing, there is data on the combination of IK-930 with trametinib (Tra) and/or osimertinib (Osi) in a xenograft model of EGFR resistant lung cancer.
Perfect. This is just what we need to see if the T-A-32 patent data line up.
Trametinib is a MEK inhibitor (MEKi) and osimertinib is an EGFR inhibitor (EGFRi). Bells are ringing in my mind.
I look back at the combo patent (‘986) in vivo data. One graph in particular stands out: tumor volumes in the H1975 xenograft. There’s data on T-A-32 as a monotherapy or in combination with a MEKi and/or an EGFRi.
Home stretch: connecting the dots
Time for the side-by-side comparison. First check: the doses match. The SEC filing has 75 mg/kg IK-930; the patent has 75 mg/kg T-A-32. The SEC filing has 1 mg/kg Tra; the patent has 1 mg/kg MEKi. The SEC filing has 2.5 mg/kg Osi; the patent has 2.5 mg/kg EGFRi.
I can hardly contain my excitement at this point. Sitting at the edge of my seat.
Next: tumor volume axes. Starting tumor volumes line up at ~250 mm3. Upper bound is 2000 mm3 for both. X-axes are a bit different (0-18 in SEC filing, 0-20 in patent) but last timepoint in both is at ~19 days. Check.
Okay the last part: shape of the graphs. There’s the same noticable gap in the graph between 1 mg/kg Tra (MEKi) and 2.5 mg/kg Osi (EGFRi) arms. For each treatment arm, I check one by one to make sure the data have the same shape in the SEC filing and in the patent. Checkmate!
Lo and behold, they line up! T-A-32 is indeed IK-930!
P.S. Those paying attention to the TEAD inhibitor space will recognize that IK-930 is very similar to VT-103, an experimental TEAD inhibitor by Vivace Therapeutics. Just a -CH2 difference!
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