IMM (ASX) Ann: Final Phase IIb AIPAC clinical trial results for Efti in MBC

Originally posted by Vivo: ↑

That article is one of the most comprehensive analysis of Immutep I have seen. The author posted this in the comments two days ago. There’s info that hasn’t been discussed here on HC re the European trial design in contrast to a US trial which would affect PFS and OS. Very interesting

”think the sell off has created a buying opportunity. Anyone that was expecting Overall Survival to be statistically significant for the AIPAC trial has not been following the company closely enough. What everyone should have been looking for in this late breaking presentation at #SITC21 was whether the 3 sub-groups --- (a) <65 years old, (b) low monocytes, and (c) Luminal --- which importantly were all pre-defined prior to the un-blinding of the AIPAC data (AIPAC was a double-blind, placebo controlled trial) did better. Indeed the OS for all three was better across the board, plus the OS for all three pre-defined subgroups are statistically significant.
Here are those details by each pre-defined subgroup:1) OS for <65 years old increased to +7.5 months from +7.1 months in Dec 2020, leading to a p-value of 0.017 and an HR of 0.66
2) OS for low monocytes increased to +19.6 months from +9.4 months in Dec 2020, leading to a p-value of 0.008 and an HR of 0.44
3) OS for the more aggressive Luminal B type of Breast Cancer increased to +4.2 months from +3.8 months in Dec 2020, leading to a p-value of 0.049 and an HR of 0.67

Another key point that was covered in the article above, which I will reiterate here, relates to the dosing in the AIPAC trial. As detailed above, the AIPAC trial was a European trial design, so the chemotherapy (paclitaxel) was discontinued at 6 months. When one takes into consideration the mechanism-of-action (MOA) of eftilagimod alpha (efti) in conjunction with chemotherapy, that MOA is the chemotherapy kills cancer cells creating cancer antigens that efti takes and presents to immature dendritic cells (DCs); then these DCs mature and spark the immune system driving CD8, CD4 and NK cell production. This is the "pushing on the gas" that the company refers to with respect to the immune system. So when the chemo, in this case paclitaxel, was pulled at 6 months efti did not have the cancer antigens available to present to the immature DCs. This European dosing regimen also very likely had an impact on the PFS of the AIPAC trial. They say a picture is worth a thousand words, and one image worth looking at is Slide 11 of the March 2020 AIPAC trial presentation deckwww.immutep.com/...).
As you will see clearly and as the company states at the bottom of the slide, the effect on PFS is quite evident as long as paclitaxel is given together with efti. When paclitaxel was pulled at 6 months, the PFS advantage in the efti/paclitaxel group shrank dramatically (see the red ovals in graphs).

This makes all the sense in the world when the MOA of efti in conjunction with paclitaxel against cancer is appreciated and understood. In spite of this inferior trial design, which very likely impacted PFS and OS, we are seeing statistically-significant OS across all three pre-defined sub-groups. Importantly, Immutep has stated they will be moving forward with a US trial design that will combine efti and paclitaxel until progression...that US trial design may lead to improved PFS as well as improved OS.
The other positive datapoint that is worth mentioning is that Immutep's partner in China, EOC Pharma, is moving forward at their own cost on their Phase 2 trial combining efti & paclitaxel for metastatic breast cancer. That decision was announced months ago. In addition to the AIPAC trial, EOC Pharma ran their own Phase 1 trial in China before making this decision, and also had the data in hand that the OS for the entire trial was not statistically significant in Dec 2020 like everyone else. Notably EOC will also be moving forward with a US based trial design vs European trial design.

Looking forward to Immutep's conference call next Tuesday at 4PM ET after its abstracts at SITC have been presented. Expecting more details across board and in particular expect to see some more data around CDK4/6 inhibitors given (1) patients with prior CDK4/6 represented ~43% of the overall AIPAC patient population and (2) the following excerpt from AIPAC's principal investigator's attribution in Immutep's press release:
"...This is one of the first trials to report efficacy of chemotherapy after introduction of CDK 4/6 inhibitors in previous treatment lines. It underlines the high unmet medical need in this patient population...".

As per Immutep's Dec 2020 presentation, prior CDK4/6 had a negative impact in the OS for the placebo group where median OS shrank meaningfully from 20.0 months to 14.9 months; however in the efti & paclitaxel group with prior CDK4/6 that did not occur and median OS improved to 20.9 months up from 20.4 months. As mentioned in the article above, these stats could attract the attention of Pfizer and others given CDK4/6 are now standard. Notably the largest selling drug in Pfizer's oncology franchise in 2020 at $5.4 billion in sales was Ibrance, their CDK4/6 inhibitor. For more on CDK4/6 see slide 11 and slide 14 of Immutep's Dec 2020 presentation...link here:

www.immutep.com/...

Finally for what it is worth, below is a link to a story published earlier today after the Australian market closed, from Australia's prestigious Financial Review titled "Why big biotechs will have their eyes on Immutep". The entire article is worth reading. It notes that "the positive results, plus the company’s 21% share price fall in the last two days could prove to be the catalyst that gets the likes of Merck, Pfizer, Novartis, Bristol Myers Squibb or Japan’s Ono Pharmaceutical to swoop sooner rather than later." Additionally it ends with a comment from Wilsons analyst Melissa Benson, who recently initiated on Immutep, "If you take a bit of a top line view of the program and don’t appreciate that Immutep had already moved on from the total [patient] group to the three sub-groups, then that is a driver [because it wasn’t statistically significant]..But we expected that. This has been a crazy over reaction. It’s an interesting buying opportunity for those that understand it.” I agree with Melissa's assessment.

Link to Financial Review's "Why big biotechs will have their eyes on Immutep":”

Expand

Many thanks @Vivo. In supplementing the discussion of does/prescription here is the last bullet point in the conclusion of the AIPAC SITC21 poster (available on IMM website):

WEEKLL paclitaxel + efti should be further investigated in a phase III HR+MBC setting.

So, seems like the expert have done their due diligence and planning for Phase III (anticipated to recruit 1H22 as i read in one of the reports - forgot which.)

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Ann: Final Phase IIb AIPAC clinical trial results for Efti in MBC, page-79

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Ann: Final Phase IIb AIPAC clinical trial results for Efti in MBC, page-79

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