Ann: IND clearance received from US FDA for CHM 1101, page-10

A meaningful progression in that Chimeric Therapeutics needed to get a new IND approved by the FDA before it could ramp up the phase 1 recruitment by opening up new clinical trial sites (note it was plural in the announcement).

For those who are unaware, a clinical trial cannot commence unless an IND has been approved by the FDA. Or in this case, CHM couldn't open up their own sites to recruit for this trial. But the City of Hope received their IND approval for this trial back in late 2019, as such they are allowed to run this trial as sponsor. What this meant was that Chimeric Therapeutics had little leverage to control the speed of the trial, with the only clinical trial site in City of Hope. That was OK for the early stages of this trial, as it would have taken some time to get the new IND in place (it's a fair bit of work) and then through FDA review (which is 30 days)... but once they get past the second cohort.. it is clear that CHM want to speed things up considerably and possibly expand the trial scope beyond18 patients, which is what City of Hope originally expected from their initial IND.

Since CHM acquired the license though it has been revised to 18-36, keep in mind most phase 1 trials are less than 30 patients... so suggesting potentially 36 (or even more) is a good thing as they can explore different dosing regiments and/or higher / less frequent/ more frequent dosing etc.. all with the goal of getting as much data to make the phase 2 trial as well designed (to maximise success) as possible. The more data you can generate at the early stages the better.. and it appears CHM is not rushing things and will be data heavy entering into phase 2, which will follow very shortly after phase 1 is complete.

Management were probably waiting for this IND clearance before they submitted their IND for the basket trial... or it may already have been submitted, based on feedback provided by the FDA to date. In any case.. I suspect we'll see that IND clearance follow in the next couple of months.

Brief overview of key events thus far in relation to the CHM 1101 trial:

November 2019: City of Hope received FDA clearance on the IND for CLTX CAR-T (now called CHM 1101)
July 2020: Chimeric signed CLTX CAR-T licensing agreement with City of Hope
September 2020: First patient dosed
January 2021: CHM listed on the ASX
April 2021: First four patients dosed in lowest dose all passed 28 day follow up without dose-limiting toxicities
May 2021: First patient dosed in second cohort (via ICT and ICV)
August 2021: CHM receives FDA clearance on the IND to develop CLTX CAR-T (CHM 1101)

High confidence of upcoming milestones between now and Dec21:
- cohort 2 CHM 1101 dosing complete
- new clinical sites (plural) for CHM 1101 opening up
- Basket trial (melanoma, prostate, colorectal cancer) for CLTX-CAR T IND submitted (and it takes 30 days for FDA to provide clearance before this trial can begin).
- Data read-out of earlier patients; patients with this level of disease severity typically have on average 5-8 months survival, not that first patient would have been dosed over a year before this data read-out, so any survivors will be a positive sign. Also keep in mind that safety is the priority and at such a low dose, no treatment benefit is expected.. but if there is outcomes such as tumor shrinkage at such low doses, then things could get very interesting.

And I'm not ruling out another product getting licensed (targeting allogeneic, novel CAR designs (3rd gen / dual antigen targets), novel NK cells or macrophages derived therapies... but more likely to be 2022.

It is rather early days for CHM, but it has already got a very impressive pipeline for a newly listed company in the oncology space. And one thing that can easily be taken for granted, but really shouldn't be.. is that timing is everything. CHM is the definition of a company that is in the right place, with the right assets at EXACTLY the right time.

There are many biotechs that have been listed for many years that had to spend several years doing pre-clinical work in the lead up to finally getting a phase 1 trial underway after years of capital raisings and dilution... and worst still, the market those products are chasing or the products being developed were seen to be too risky.

So here we have CHM who has in its FIRST year of listing having hold of assets such as CHM 1101 which was already in a phase 1 trial, and CHM 2101 which will get its IND to start a phase 1 trial in 2022 ... what that means is that CHM has been able to by-pass approx a decade of research and pre-clinical work for each of those assets (so approx 20 years saved). This is only possible because the CAR-T field has been validated through five FDA approved CAR-T therapies, all in blood based cancers... so the 'technology' is proven... and it is now the hottest field in biotech. This didn't happen overnight, and it is the culmination of decades of research and development that we find ourselves at the start of a new era in oncology... CAR-T therapy is very successful with blood cancers.. but it is only now that we are seeing investment dollars pouring into CAR-T therapies that aim to cure solid cancers.

So from a shareholder perspective, being invested in a company that is in the 'right place, with the right products at exactly the right time' simply means that the potential return on capital is maximised. Dilution is guaranteed, but in CHM's case... it will be done when the market cap is substantially higher than if it were only at pre-clinical stage, or in phase 1 where a field that is not proven / seen to be too risky / market does not attribute value to early success.

Right place, with the right products at exactly the right time = earlier success = market places high value on success = higher valuation = less dilution = higher return on investment = happy foundation shareholder.

Goodluck all