Clene Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Thank you, Alexa. Appreciate the invite. Clene is a clinical stage nano biotech company. We have been in existence for 13 years. That entire 13 years has been a big adventure, taking our asset to now, at the final stages of a new drug application that we will soon be submitting to the U.S. FDA for the treatment of ALS on the accelerated approval path. Just a little bit of insight. Our lead asset is a nanotherapeutic. People drink it by mouth orally. If I was blindfolded and took our asset versus this glass of water, I would not know a difference. Tastes like room temperature water. We have now hundreds of people that have had access to this asset. In fact, we have over 1,250 collective patient years of experience.

900 people have been taking this asset and hundreds are presently doing so in a compassionate use expanded access protocol, four of which have been approved by the FDA, three in ALS, one in multiple sclerosis. What our asset does is drive the energy necessary to the failing neuron. You and I are highly bioenergetically needy with respect to the way our neurons control everything that we do, the way we move, walk, talk, eat, chew, breathe. By consequence, what our asset is doing is driving important bioenergetic metabolite nutrients, while also reducing reactive oxygen species and driving neural function through supporting the mitochondria. That is a big mouthful. Effectively, your brain and mine is only a small portion of our body weight, but it is consuming a quarter of our energy.

In a patient that has ALS, of which there are 35,000 in America, and of which there are many other thousands worldwide, they still, once they get this diagnosis, are given a uniformly fatal diagnosis. Clene is now at the final stages of just wrapping up a new drug application, which, as I said a minute ago, we will be soon submitting. We will find out hopefully by the end of the year, whether or not the agency will give us a PDUFA date, commencing thus six months of review, an answer of which we hope to receive from the agency as to the possibility of commercialization, sometime June, July next summer.

We've completed two phase IIs in ALS, one called RESCUE, and the one you just mentioned called HEALEY, is with Dr. Marisa Govic and her colleagues at Harvard University, as well as more than 50 clinical sites countrywide. The HEALEY study is really the anchor program by which the agency is considering this. Alexa mentioned that we missed the primary endpoint, ALSFRS, as has every other of the seven remaining programs that are thus concluded in HEALEY. Clene is the only of these 8 different programs, 8 different drugs, that achieved the secondary endpoint of survival. We're the only of the 8 different drugs that achieved the exploratory endpoint of clinical worsening, and we're the only of 8 different drugs that achieved a reduction statistically significant in a phase II double-blind placebo-controlled study of the biomarker neurofilament light.

Why that becomes very relevant is because Biogen received an approval a few years back for their SOD1 ALS asset. Just to distinguish, there's 35,000 Americans with ALS, roughly. A small percentage of these, estimated to be a few hundred, have a genetic component of ALS called a missing SOD1 gene. Biogen developed a wonderful asset called tofersen that enables a replacement for this missing gene. Though they missed the primary, secondary, and exploratory endpoints in their phase II study, they nonetheless achieved demonstrable neurofilament drop. What we've done is gone into the agency for heterogeneous disease, which is the 98% of the rest of the ALS, and asked the agency if they would consider the possibility of a surrogate-based, in other words, neurofilament reduction, approval process in that respect. So HEALEY becomes very much the anchor, and there's some critical pieces here.

The agency came back to Clene, and we'll jump more, Alexa, later to the regulatory strategy, but it's important just to give a sense of design. When HEALEY recruited, there was 3 arms that were recruited all at the same time, and the other two assets in two different regimens were not positive, but the agency asked us to look back at that data and to see if we could use this as a comparable control. Namely, because the agency has not been enthusiastic, and we have lots of different examples and many different drugs on natural history. Since all the assets were randomized with the same inclusion, same exclusion, same trial design, same protocol, and same follow-up for nearly 4 years, this becomes a very interesting data set to look at, and the agency's asked us to really explore that extensively.

First, let's maybe give some, if unfamiliar to the audience, what neurofilament is.

Yeah. Great. Neurofilament stands for neurofilament light.

This is molecular weight, not as in sunlight, molecular weight. As the disease ALS, or for that matter, any other neurodegenerative disease, attacks the neuron, it leaves behind a bit of a debris field, a cytoskeletal protein remainder of the damaged and destroyed neuron. I can measure it in my blood, I can measure it in my CSF, my cerebral spinal fluid. Neurofilament has really emerged as the surrogate to understand and to follow. This has been evolving for some years now. That neurofilament light, as I mentioned earlier, Clene remains the only phase II program to see statistically significant difference in neurofilament.

Now modestly, in heterogeneous disease, we didn't have the same benefit as was seen in the tofersen case, just to be clear. That is really the key question in front of the agency is, does a modest neurofilament light reduction matter? Let's go back to the essence of your question, and I'll come back to that second question, is that we saw a neurofilament drop of about 10%.

To Alexa's point, we received $45 million to pursue a significant expansion of our compassionate use program from the NIH. There was an act that I AM ALS and other patient organizations championed called the ACT for ALS. It was $500 million that Congress provided for research and for compassionate use. Clene received nearly 10% of that. That enabled us to actually give to, let's see, 300-plus people, our asset for compassionate use. Neurofilament was tracked through the duration of that program. So when we were in front of the agency asking them if they would consider survival as a surrogate, they said, "That's the definitive endpoint. We would define survival as the essence of your primary for your phase III confirmatory, but really we don't have a path for survival as a surrogate.