Corbus Pharmaceuticals Holdings 3rd Annual Guggenheim Healthcare Innovation Conference

Yuval, welcome. Morning, Paul. Thanks for having us here.

With pleasure. Corbus is based in the Boston area. We are a small company. There is about 40 of us or so. We are a drug development company, and we have a pipeline that, as you said, is out of the ordinary because we have two assets that are just completely unrelated to each other. The one asset is an oncology asset. It is a Nectin-4 targeting ADC armed with MMAE, so conceptually the same logic as PADCEV or enfortumab vedotin. It is quite late stage in terms of its development. We have just launched its phase III registrational study in second line oropharyngeal. Like so many of the ADCs these days, this one too is a partnership between a U.S. company and a Chinese innovative company. This one comes from CSPC in China. The second asset we have could not be more different.

It, first of all, is a small oral molecule, once-a-day pill. It's not at all in oncology. It's actually in ObesityWeek, and it is a mechanism of action that is, in a sense, a comeback story. The mechanism of action is an inverse agonist of the GPCR known as CB1. This was 20 years ago a highly sought-after, high-visibility mechanism of losing weight. It had some major obstacles thrown in its way, and now it's having a comeback with us being sort of at the forefront of that. And that too, Paul, is in the clinic, as you know, and just completed a, technically it's a phase I-B, but it's a pretty large one. It was a four-month in total, three months of dosing, once a day, double-blind placebo-controlled with about 250 patients.

With pleasure. I'll start by, first of all, maybe a little bit on why this is different than PADCEV. The idea is not to come up with a biosimilar to PADCEV, but rather with something that improves upon the design of PADCEV. And so, conceptually, it's quite simple. It's take a Nectin-4 targeting ADC armed with MMAE like PADCEV, but make it considerably more stable. And so the ability to hold onto the warhead for much longer, meaningfully longer, translates into a very different safety and tolerability profile, where what has been engineered out or down to a minimum are peripheral neuropathy and skin, which are the sort of the issues, the friction points, more than friction points, or really the drawbacks of using PADCEV. Once that's been established, then the question, Paul, is what do you do with something like that?

The way we approached it was, at least as a starting point in clinical development and commercialization, not to try and compete with PADCEV. That would be very ambitious for a company such as ourselves. The swim lanes that we found were other types of solid tumors in metastatic settings that are known to be highly enriched in Nectin-4. The two that we are exploring, the first one, as you mentioned, is oropharyngeal. It is the third most Nectin-4 enriched tumor type. PADCEV has shown very promising data there as well, but again, always hindered by their safety and tolerability profile. We are moving forward and have started, as I said, a phase III study. The second tumor type we focused on is cervical cancer. Again, very, very enriched in Nectin-4.

I believe it's the second most enriched Nectin-4 tumor, and that's where we have maturing phase I data.

For sure. Let's start with the second line because that's where we're in phase III, as you mentioned. Second line head and neck in general is a really acute unmet medical need for patients at the moment. There really is very, very little available to them. Our own data analysis has shown that probably close to half the patients elect not to have anything done to them in second line because the options are just so modest in terms of efficacy. There, what we have shown is in the oropharyngeal subset of head and neck, which is usually associated with HPV positivity, right? That's a type of head and neck tumor type that is driven by HPV rather than the other forms of head and neck, which are typically driven by smoking and drinking.

In that tumor type, what we've shown is monotherapy second line plus in a maturing dataset of phase I was an objective response rate of about 43% durability, and again, just a very, very satisfactory minimal levels of peripheral neuropathy and skin. That one is in phase III. That is our TEMPO-1 study that has started. What you've alluded to, Paul, is the possibility of going beyond just the second line plus setting in oropharyngeal, in our case. There, the most sensible one would be what happens one step before that in frontline. In that sense, it's merely emulating what, back in the day, Merus did with Peto, starting in second line and then moving to frontline. For that matter, what back in the day was done with PADCEV in bladder, second line first and then moving into frontline.

The frontline being, of course, in combination with pembro, which would be standard. That dataset, which is an exploratory dataset, should mature enough for us to look at in the first quarter of next year. That will be very, very interesting, because if that is the case, then that obviously opens an even larger market opportunity.