AIPAC and Efti; My Final Take

We are extremely close to AIPAC, so I thought I'd put my full take on the trial and Efti.

In the Ph1 MBC trials undertaken by IMM, there were some very compelling results in regards to patient responses. Side effects were quite good, so not focusing much attention there. Of the 30 patients who qualified for assessment, 27/30 had not progressed after 6 months. This means that Efti & Paclitaxel (referred to as Pacl from here) led to a very durable response in patients, keeping tumours under control for at least 6 months. Of note, this was achieved at very low dose levels of Efti (6.25mg max I believe). Also, 87% of patients responded, with an ORR of 47% I believe. This means that 47% of patients had their tumours shrink by at least 30%. However, ORR and DCR are not the best proxies for PFS, as tumours can shrink or stabilise, thus qualifying for either of the above metrics, then regrow, meaning its PFS could be short. Therefore the focus is on the durability of the response, with 90% not progressing after 6 months. In the Ph2 run in study, all patients responded at the 30mg Efti dose, which is the dose for the Ph2b trial. Similarly, 87% of patients had their tumours stop growing at some point in time. Therefore, we have our first sign of a replicated benefit of Efti & Pacl in MBC patients.

Interestingly, in a Ph3 study of patients with similar tumour stages, the median PFS on Pacl alone was 5.6 months. Meaning >50% of patients had their tumour progress after 5.6 months. A very large disparity from the IMM results. Furthermore, this 5.6 month read was for patients with a median age of 55, and <3 tumour sites. For comparison, IMM's Ph1 was run in patients with a median age of 64, with >3 tumour sites. Worse off patients, better responses. Quite compelling. One could make the case that if the playing field was level in terms of patient characteristics, the combo would fair even better. Also, in the medical journal regarding the Ph1 trial, it makes note that chemo patients, if they are going to respond, it will be in the first 3 months. However, with the Immuno combo, patients not only respond in the 1st 3 months, but they continue to respond to subsequent months. Some patients even remain stable for quite some time, then their tumours begin to shrink. Durable response.

In the Melanoma Ph1 trial, and the Tacti-002 trials, we have again seen results confirming deep, durable responses. Efti, when combined with other drugs (Keytruda and Pacl), leads to a sustained response across multiple indications. This is very critical as PFS is all about the durability of the response and delaying progression as much as possible. We have seen it in 4 tumour types. This is no fluke, reproducing results like this goes a long way in proving Efti leads to a sustained response.

The big variable though, is all the aforementioned MBC data is for patients who have not received CDK4/6 Inhibitors such as Ibrance. This type of treatment was only recently approved, and thus, all patients in AIPAC would have previously been on Ibrance. This treatment does quite well at increasing PFS, therefore one could think that patients who have progressed on this type of treatment have more aggressive and resistant, harder to treat tumours. Not much investigation has occured into treatment after progression on this type of drug, however one trial has shown that median PFS on Chemo is only about 3.6 months. However, OS after treatment on CDK is about 24 months, meaning patients live for about 2 years. To me, this indicates the tumours are treatable to an extent, and not past the point of no return. What we do know, is that Chemo is next to useless in this field, and therefore the IMM team is anticipating a PFS on the Pacl arm of approx 3-4 months, which would come as no surprise to me. The big question is, whether Efti and Pacl can maintain its great results, and produce a median PFS of 6-7 months. I believe it is possible - CDK will play a role in this trial, but not to the point it shows Efti & Pacl isn't that great. I don't think the tide can turn that much and median PFS in this arm will be sub 6 months.

Regarding the EMA, they have essentially stated they need a trial with high integrity (tick, double blind), better QoL and safety (tick), and an increase of 1.5 months in PFS - anything in excess of this would be a very big win. I for one am anticipating an increase in PFS of 3-4 months over the control arm. From this, IMM can make a very strong case for approval in Europe, and use the AIPAC data to leverage their case in the USA.

If it's positive, we are off to the races. Fair value off good data? No idea, but it really depends. If we get p < 0.001 or something ridiculous, with a 3-4 month PFS gain, it won't take long for the SP to run past $2. If the data is negative, the downside is covered by good results in all other cancer treatments they are exploring.

I know people have said the company would like to pursue licensing options, but if the price is right, this company will be acquired by years end off the back of AIPAC. For what price? Couldn't tell you, but it'll be in the billions.

I await AIPAC with great interest.