Clene Inc. Common Stock Canaccord Genuity's 46th Annual Growth Conference

Interesting, because we've just had five meetings with the agency, the most recent of which was in March. We announced on May 3rd the outcome of that meeting. To be entirely candid, we walked into the meeting not exactly sure where the agency was. We heard from them previously that our survival data, which they have understood clearly, cannot work by and of itself for the possibility of accelerated approval. They've said pretty clearly that survival alone is not a surrogate biomarker, survival is not a biomarker, and that there needs to be a biomarker. In the spirit of that, they asked us to go see if we could see concordant biomarker data elsewhere, and Clene announced that we did so with the $45 million funded expanded access protocol that NIH gave us from the Accelerating Access to Critical Therapies for ALS Act.

We have this concordant data set between the HEALEY data set during the placebo double blind, and the EAP, where we both dropped neurofilament light in both cases about 10%. After the presentation at the most recent meeting in March, I was accompanied by Jinsy Andrews, who runs the NIH-sponsored EAP, by Dr. Merit Cudkowicz, who was the primary clinical investigator here in Boston of the HEALEY program, and by Dr. Robert Bowser, who is one of the world's experts in neurofilament light and its biomarker impact and has testified on behalf of other companies at the agency around the same thing.

After the presentation of the three of them, I basically asked the FDA, "What would you best like us to do?" Because we had received just a few days previous to the meeting, pre-meeting minute notes that I have here in my hand, and I will read it directly. The proposed data may be capable of supporting the submission review of an application under the accelerated approval for the treatment of ALS, but, and that is an important but, you need to demonstrate not only the substantial evidence of effectiveness of an effect, that is exactly how they phrased it, the effectiveness of an effect on CNM-Au8 neurofilament light, but also that the modest magnitude, this 10%, of the change, modest magnitude of change in neurofilament is reasonably likely to predict clinical benefit.

Then for the next three pages, they gave us a number of, shall I call them breadcrumb trails, things they wanted to see. For the last three months, we have been working extensively on that, and we announced that data yesterday morning. Just to give a little bit more context from the meeting, this is a long answer to your first question, Sumant. The agency basically told us at that meeting in March, "Is 10% clinically meaningful? That is the key question. We are not exactly sure. That is the reason we want this opportunity to accept an NDA, review it, dig into the data, but to really see how neurofilament light is tied to clinical benefit." Those comments, plus the comments in the divisions minutes, gave us the data we announced yesterday.

Sure. First of all, for those of you that are not familiar, this is the asset. This is an oral suspension of nanoparticles suspended in water. If I was to be blindfolded and drink a glass of water versus this asset, I could not tell the difference. It would taste like water because it is primarily composed of water. In this are trillions of nanocrystals at 13 nanometers in size on average. That is small enough to come into my gut, cross into my bloodstream, and cross up across the blood-brain barrier. We see evidence of these nanoparticles in the tissues of the body, including the eye, the spine, and the brain in animal work. What is going on is we are driving a bioenergetic metabolite change in the failing mito.

In the case of ALS, for example, in neurodegenerative diseases generally, but ALS in particular is where we have really staked our primary claim, the neuron is under such stress and such distress that it is completely compromised, and by consequence, it dies. When it dies, it leaves a cytoskeletal protein remainder in the bloodstream, which we can measure. That leads us to the neurofilament biomarker thesis. Back to the primary point, this is an intersection of physics and material science into biology. It is not classically chemistry in any way. The nanoparticle is serving as a catalyst to drive a decrease in reactive oxygen species, an increase in nicotinamide adenine dinucleotide, as well as ATP, adenosine triphosphate, two of the essential building blocks that are driving what energy is required regardless to drive function.

What we are really working to do is to see if we can keep that neuron, despite the assault of the disease, effective and able to not just fight back against the disease, but to keep function. By function, I mean, in the case of ALS, that would be a survivor driver, cardiac and pulmonary function. That leads us to a key question. We are often asked, well, why is there not other function besides just survival? That is really what happened yesterday, which is I think quite notably the case, is we found yesterday in this work we have been undergoing for 90 days to look at neurofilament and its trajectory, that if in fact we look at functional benefit, we found that we were quite concentrated in neurofilament stabilization or declining subjects, that is to say, where the drug helped the neurofilament.

And in that case, we do see an ALSFRS statistically significant benefit and also breathing capacity through slow vital capacity. Now, both of these were post hoc because both of these were addressing exactly the question the agency asked us to pursue, is we need to understand against concurrent control sets, not natural history, if you've got an effect.

So we just did that assessment using actually natural history, where it applies, looking at people who never got any of our drug for certain. And we have a decade about of data in more than 2,000 subjects across the Answer ALS and the APST datasets where ALS researchers have tracked survival and function as a natural history set. And we found, looking at that dataset, that 10% reduction, though seemingly modest, does have a survival link, and it was P0001 and P001 with respect to the two different studies. There's an asset that the agency approved on neurofilament alone, from a company here in Boston only a couple of years back in SOD1-ALS, which constitutes 1%-2% of ALS subjects. Clene is not applicable for that indication. We're not going after SOD1. We're going after the rest of the disease.