No thoughts specifically on Opthea @thetjs however because these ETFs are open ended, they are always buying the underlying shares as people buy more of their ETFs, so passive inflows always means more buying. If it was an ASX-300 tracking ETF, then it matters whether Opthea is in or out of the index obviously, and it also matters where they are in the pecking order of the index, because an ASX300-tracking ETF must reflect the underlying index weightings - unless it's an equal-weighted ETFs but they represent only a small minority of ETFs. The majority of trackers need to keep their weightings proportional to the index weightings of the index they are tracking coz if they didn't do that they wouldn't replicate the index returns (less their modest fees).
However, with some of those other ETFs that aren't tracking the main indices but are instead tracking broader global indices like that FTSE global shares index I mentioned that one of Vanguard's ETFs track, the underlying FTSE broad global shares index might not balance too often, they might just rebalance occasionally, like annually, six-monthly, 3-monthly or monthly, based on whether the companies still remain within the largest x number of companies in their investable universe (that passes their ESG filters in this example) - so in that respect, big movements in market caps of these companies (like Opthea) relative to the rest of the companies in those indices is relevant.
So, short answer is if it's an ETF that is tracking the ASX300 index, they will be rebalancing as Opthea's index weighting changes, however many other ETFs would rebalance less often based on Opthea's market cap, but in terms of ETF inflows and outflows, these ETFs are always (like on every single trading day) buying and selling shares in the companies that are held within those indices based on people buying/selling those ETFs (net inflows/outflows).
In terms of substantial shareholder ("Sub") notices, the ASX only requires them to lodge a notice:
a. When they go from below 5% to 5% or more (a "Becoming..." notice);
b. When they remain over 5% but their shareholding moves by 1% or more of the company-they-are-holding's SOI (a "Change in..." notice); and
c. When they go below 5% (a "Ceasing to be..." notice).
All of those notice require a daily summary of share movements (buys and sells by the "Sub" in the company they are lodging the notice for) for the entire period since the previous notice was lodged by the same shareholder, so daily movements won't be disclosed UNTIL one of those three events occurs, and then you get the full list of daily trades since the previous notice. So there's usually plenty going on in the background that we don't get to view the details of until one of those notices is required to be lodged.
Also, because ETF managers are not worried about share price volatility, they do not consider liquidity when placing their buy and sell trades, meaning they don't care how much it moves the share price, but most of the indices that they follow (such as that FTSE Global ESG Ex-US All-Cap index that I mentioned that would have Opthea as a constituent) do have some liquidity filters in place in terms of what they hold, so both market cap minimums and average daily volume traded would be taken into account. But that's the index, and the index doesn't buy or sell anything, it just adds and subtracts names and moves them around (weightings or position rebalancing). It's the ETFs and mutual funds that track that index that do the buying and selling, and they don't care if they move the share price significantly - they just follow the index - and also buy and sell based on their net inflows/outflows from their ETFs/mutual funds.
The very short answer is that passive money flows do distort both market valuations (share prices) and volatility (share price movements) in a lot of cases, and are another reason why the efficient market hypothesis is a load of steaming horse manure.
If Opthea does well, they'll move up the S&P/ASX index ladder (next stop: ASX200) and they'll get added to more ETFs and their share price will be higher, and if they drop out of the ASX300 again, the opposite will happen. And in between those events, they'll move around based on investor sentiment - which hopefully will mostly be based on the company's underlying prospects and progress - and also they'll move around on passive fund flows - meaning ETFs and mutual funds buying and selling which they do daily based on net inflows/outflows to/from those ETFs by passive investors - which are mostly impacted by general market sentiment - i.e. whether people want market exposure or not at any given point in time, how much exposure they want, and to what.