Preclinical results for triple a combination treatment were presented at the AACR in April 2023. In a CT26 mouse model (colorectal carcinoma cell line) mice treated with the triple-combination had a significantly lower tumour volume as can be seen below.

Double combinations were also tested in other experiments. The standard deviations for fostrox-Lenvima and fostrox-PD-1 combinations were quite high, so the synergies were not significant in these combinations. The fostrox-PD1 combination had worse results than PD-1 alone. The reason for using a colorectal cancer model, as explained in the conference call, is that the level of DNA damage is very limited in human liver cancers (HCC) while it is high in syngeneic mice models of HCC. Therefore, the colorectal model, having little DNA damage, is more representative (the mode of action of fostrox is creating DNA damage). The results thus suggest that a triple combination could be highly synergetic.

Some early results from the phase Ib part of the trial of fostrox were presented at the conference call. One patient was still on treatment with fostrox (20mg) and Lenvima after 8 months after progressing on a first-line treatment of Tecentriq and Avastin. Another patient was still on treatment after 6 months with fostrox monotherapy (30mg, and not part of the dose escalation cohort) after progressing on Tecentriq and Avastin. This latter results shows fostrox has clinical benefit in at least some patients.

The reason for the quick recruitment in the Lenvima + fostrox arm is that the first line has become Tecentriq + Avastin while Lenvima is the preferred second-line treatment. As there are no reasons for believing there to be negative interactions between Lenvima + fostrox, one would at worst expect extra side-effects with little clinical benefit, so it makes sense to want to participate in such a study. Further development in this setting makes clinical sense. PD-1 treatments are less popular in the second line. The fostrox + pembro arm is therefore strategically less important in the short term (though it would be important to have results with this combination for future developments and as a control arm).

Tango Therapeutics also presented new data at the AACR conference demonstrating single agent activity of USP-1/TNG348 as well as strong synergy with PARP inhibitors in certain models. The intention is to start a clinical trial in 2023.

Costs were in line with the previous quarters, as is evident from the graph below.  Total operating costs amounted to SEK20m. The cash flow was SEK-17m; cash and cash equivalents amounted to SEK101m (SEK118m). It was mentioned in the conference call that it should last into Q2 2024. The company considers this to be sufficient to complete the ongoing phase Ib study as well as one combination arm in the phase IIa expansion part. This means we may have to factor in some dilution if the company decides to continue with the pembrolizumab, which it has not yet decided.

We only make minor changes to our estimates adjusting the timing of some costs. This has no significant impact, and we reiterate our Base Case of SEK15. However, we may factor in some moderate dilution for the phase IIa part with Keytruda depending on what decision Medivir takes concerning this arm.