$ALEC investment thesis build-up: Analysis of AL001 and AL002 clinical trials

I’ve spent some time looking at a company called Alector ($ALEC) in the last few weeks. Alector is a biopharma company focused on the AD and FTD indications. I thought I would share some useful information regarding the clinical trials for AL001 and AL002 as well as give my analysis on them. 

Clinical trials 

Alzheimer’s disease 

We’ve seen AB targeting immunotherapies fail in meaningful efficacy in recent years. I found Alector’s pipeline refreshing in that, although it is another mAb, AL002 targets neuroinflammation which has been gaining more and more respect from the scientific community as the root cause of Alzheimer’s Disease. If the efficacy is there for AL002, we could see revenue figures for the likes of Humira. 

A quick rundown of AL002:

INVOKE I

Data is currency in this industry and for now, we do not have much to go off of for AL002. We did receive some phase I safety data in Q4 of 2019, which showed that AL002 was well tolerated in all interventions as compared to placebo. One thing I found interesting about this data is that the frequency of nausea jumps from an average of 0.4 in the 0-45 mg groups to 6 in the 60 mg group. 

INVOKE II

In terms of the phase II setup, nothing drew too many red flags. The primary endpoint is CDR-SB with secondaries for MMSE, ADAS-Cog, ADCS-AD-MCI, and safety. The 2 sites in Argentina seem strange but they have plenty of other locations in the US to compensate. Inclusion criteria was MMSE 22, CDR 0.5-1, RBANS DMI <=85. 

The interventions are 60mg, 40mg,15mg, and placebo. It’ll be interesting to see if the 60mg is worth the increase in Nausea mentioned previously in the coming data readouts. 

Speaking of data readouts, Alector is expected to announce top-line phase 2 results for AL002 sometime in 2024.

FTD-GRN,C9orf72

Frontotemporal dementia is an exciting indication for Alector. There are currently no therapeutics approved for FTD which gives Alector the first mover advantage if AL001 is approved. At this same time last year, GSK penned a deal with Alector for AL001 valued at $2.2 billion in total. $700m upfront, $500m in Q321, $200m in Q122, and $1500m in milestones. In return, GSK will share revenues equally in the U.S. and double-digit royalties internationally.

INFRONT II

Topline data was as above. GENFI is a study from the genetic frontotemporal dementia initiative, which is a group of research centers across Europe and Canada focusing on genetic FTD, coordinated by professor Jonathan Rohrer. The difference between the AL001 and GENFI data was as follows

• 3 Months: 0.5 
• 6 Months: 1
• 9 Months: 2.3
• 12 Months: 3.1 

This data was promising, with a 48% therapeutic benefit at the end of 12 months in an indication with no known therapeutics AL001 has the potential to be a moonshot. A perspective that GSK undoubtedly saw when offering the $2,2 billion deal. While promising, there are still doubts. Only 12 patients were tested in phase 2 and the 95% confidence interval ranged from 1.38 to 5.28 by the end of the 12 months

Safety data demonstrated that AL001 was well tolerated as shown below:

Baseline characteristics showed no red flags as shown below:

INFRONT III

Phase 3 has already started in the summer of 2020, and we saw nothing to note in terms of study setup. This study will be significantly larger than INFRONT II with a population of 180 patients. Phase 3 topline data will be announced at the same time as AL002 readouts (2024).