An update from the professor. Thanks for sharing @microcapguru.
I just finished reading a paper discussing the clinical impact of checkpoint inhibitors on colorectal cancer (CRC). Much thanks to Kierancrowe for posting the link. If you're interested, the title is "Review of PD-1/PD-L1 Inhibitors in Metastatic dMMR/MSI-H Colorectal Cancer". But make sure you have tissue paper for the nose bleed you'll get reading it . The paper talks about how CRC patients, who are on the whole resistant to immunotherapies (sounds like the bile duct cancer case, eh). However, it goes into detail about the clinical benefits of treating CRC patients who have the MSI-H biomarker with checkpoint inhibitors (like PD1-Vaxx). Here's a relevant snippet from the abstract:
"While the field is rapidly evolving, PD-1, and PD-L1 inhibitors have a leading role amongst immunomodulatory agents. They act against pathways involved in adaptive immune suppression resulting in immune checkpoint blockade. Immunotherapy has been slow to impact the management of this patient population due to disappointing results, mainly when used broadly. Nevertheless, some patients with microsatellite-instability-high (MSI-H) or mismatch repair-deficient (dMMR) CRC appear to be susceptible to checkpoint inhibitors with objective and sustained clinical responses, providing a new therapeutic option for patients with advanced disease."
This paper provides meat-on-the-bones for my previous assertion that patients with the MSI-H biomarker "have tumors that should be much more amenable to treatment by checkpoint inhibitors, like PD1-Vaxx". It strengthens my argument about the approach IMU is likely taking: positioning PD1-Vaxx strictly for CRC patients with advanced disease that have the MSI-H biomarker. Like Azer Cel, carving out a very defensible niche market with accelerated approval pathways. IMO, they will use this biomarker as a key surrogate endpoint for their accelerated approval FDA application. Remember, a surrogate endpoint is required for FDA accelerated approval.
This paper clearly lays out the scientific rationale for the biomarker's use as a surrogate endpoint. Importantly, an endpoint correlated with enhanced overall survival odds for CRC patients treated with checkpoint inhibitors. So IMU's next step would be to generate clinical trial data from patients with this biomarker. It seems to me now that the upcoming PD1-Vaxx phase 2 trial (Q1 2024) will be designed to deliver this data. If I'm right, the PD1-Vaxx phase 2 trial will be either a single arm study--enrolling patients with the MSI-H biomarker--or a two arm study, enrolling both MSI-H and non-MSI-H CRC patients (the control group). And if we are so lucky this trial will end early--with FDA-approval--as soon as patient data validates the surrogate endpoint. Knock-on-wood, and if the gods favor us, PD1-Vaxx could be on the market as soon as 2025. With only a single small, cost-effective phase 2 trial.
It should be noted that the current Imprinter lung cancer trial combines PD1-Vaxx, an anti PD-1, with Roche's atezolizumab (TECENTRIQ), an anti PD-L1. Clinical research has shown this to be a very powerful combination. So I've been expecting very good results from this study; much better than the initial P1a trial (remember, we still have a patient that's cancer free, years after treatment). With any safety questions answered by the Imprinter trial it's possible that the PD1-Vaxx phase 2 trial could see this combination used to treat CRC patients. This could bode very well for the MSI-H CRC subpopulation; but they may also find some encouraging results even for the much larger non-MSI-H CRC population. This would be a tremendous commercial win for PD1-Vaxx.
IMO, the flashing red light in all this was their switch from trialing PD1-Vaxx in lung cancer to CRC. Especially when you consider the time they spent and the outstanding results achieved from this trial. But here's the kicker: there is already a first and second line standard of care option for lung cancer. A much tougher battle to speedily get PD1-Vaxx approved for this indication. However, CRC--like bile duct cancer--is fairly resistant to immunotherapy. Nonetheless, the clinical benefits outlined in this paper would suggest that PD1-Vaxx has a good chance to significantly improve the overall survival odds for CRC patients with this biomarker. The upcoming PD1-Vaxx phase 2 trial could provide all the evidence needed to justify early FDA approval.
And like the bile duct cancer indication, the subpopulation of CRC patients with the MSI-H genetic defect is relatively small. But this is besides the point. Once approved, oncologists can prescribe PD1-Vaxx off-label for other cancer indications. Especially lung cancer which has a backlog of positive clinical data demonstrating its effectiveness. IMO, it wouldn't take long for other oncologists to try this new "drug" for their terminal patients once word gets out. Remember, due to its incredible safety and tolerability profiles, PD1-Vaxx can be combined with the other cancer's SOC. So there's a very low risk for a terminal patient to give PD1-Vaxx "a try". And just as important to shareholders, a FDA approval would do wonders to boost our share price. Especially an early FDA approval.
I see the new CMO's hand in all this. He and Leslie now do joint interviews. I believe it will only be a matter of time before Leslie passes the baton and he goes solo, as the public face representing the science. It appears we now have a very experienced doctor/researcher/clinician driving the direction of IMU's clinical programs. Aligning the science with short-term commercial objectives. The IMU team has laid out an impressive series of clinical trials designed to rapidly generate the data necessary for early FDA approvals. They seem to be on track, with a clear destination in mind and a full head of steam.
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Just to be clear, everything that I've written here is speculation on my part. They're not facts, just supposition. Something to chew on. While I've outlined a compelling narrative it is just that: a narrative. Not to mention any factual errors that may crop up due to my basic understanding of the underlying science. There's a mountain-size trove of unknowns between now and then. We're just going to have to wait to see how things actually turn out. That said, it's my sense that 2024 is going to be an exciting year for Imugene.
(20min delay)