Ok. I've found it from
@LeftYahoo - so which one can trump us?
BTW - Sorry, @LeftYaho I'm on my phone. I couldn't easily include your link.
1. Ruxolitinib (Jakafi). As many of you may know, this is the small molecule that has FDA-approval to treat adult GvHD. It's manufactured by Incyte, a Delaware company on the move in terms of pipeline and market cap, which is $21B. Jakafi started a 500-patient phase 3 trial on May 8 with an estimated primary completion date of July 29... hard to believe they'll get done that soon because so far they have only 1 recruiting site listed - in Pittsburgh of all places. Nevertheless, Incyte is clearly in the race. The biggest drawback for their molecule is the long, long list of side effects that will not play well in the C-19 ARDS population: Serious infections, anemia, low platelet counts, low white cell counts, liver toxicity, the dreaded neuro complication PML, and even cancers. Plus there are a host of meds that can't be given concomitantly, and no grapefruit juice - which eliminates the study for me even if I'm unconscious. They're taking patients with a higher P/F than rem-L, anything under 300, suggesting they're trying to recruit patients before they get too, too sick and can't tolerate the medicine. INCY is always listed as an acquisition target and management is aggressive and savvy. I consider them a competitor. Worth keeping a watch on even if their molecule is a long-shot for this particular indication (they're also a competitor in the adult GvHD space, obviously).
2. Athersys MultiStem. The company has a market cap of $596M and has started an open-label lead-in phase 2 to their planned pivotal phase 3 which will enroll up to 400 patients. They're using an adaptive design which allows "sequential enrollment" and more frequent interim review. As I mentioned before, they are considered number two in the cell-based therapeutic space. Their phase 2 began on April 29. They have two hospital centers listed for recruitment, both in Cleveland where they are headquartered (and where MSC's got their start with Dr. Caplan). If they match Mesoblast's speed they should move in to phase 3 tomorrow. I'll be surprised, Athersys has been a slow-walker getting in to phase 3, may have less potent cells (MAPC's), may be stepping on Mesoblast IP. Their enrollment criteria pretty much match Mesoblast's, so they're in our space, but well behind now due to failure to do an EAP. They just did a $50M cap raise through BoA/Merrill Lynch so will probably be getting analyst support on that front. The sequential design is the one variable to consider... doubt FDA would let them undercut our 90 patient interim review, they may not have enough cumulative patients for safety (global total) but we're in the Age of Covid-19. Surprises are always possible if they show exceptional results during the lead-in... Worth watching.
3. Biohaven Vazegepant. The company has a market cap of $2.8B. This is a different one. It's an intra-nasal administration of a "Calcitonin Gene-Related Peptide" resceptor blocker that's in trials to treat migraine headache. They've gotten FDA authorization to do a phase 2/3 trial and list two prestigious recruiting centers: Georgetown Hospital in the nation's capital and Thomas Jefferson University in Philadelphia. They're recruiting patients with pneumonia prior to intubation with a goal of preventing intubation. Not directly in our space but off-beat enough that I thought I'd mentionn it. Ease of administration and a larger potential population base could allow faster recruitment. It's made my watchlist.
4. Roivant Gimsilumab This is a Swiss company founded by Vivek Ramaswamy. Still private as far as I can tell. The molecule is an anti-GM-CSF mAB, so targeting as an immune modulator "to reverse cytokine storm". They have 11 prestige medical centers recruiting patients on HFNC or within 72 hours of intubation. Phase 2, 270 patients. So, they're putting a lot of dollars into this. The trial started on 4/12 and lists an expected primary completion date of July/2020. Most interesting are the trial endpoints: Mortality at 43 days, and all the secondary endpoints are measured at 43 days... The company is said to have raise $1B in PE in 2019. Definitely on my watchlist, though I think the molecule is only part of the solution to CS. Trials will tell.
5. Cytodyne Leronlimab The company has a market cap of $1.55B. The molecule is an anti- CCR5 inhibitor for which they just filed a BLA after 13 years of testing against HIV. FDA acceptance for priority review pending. They are now moving aggressively in to the C-19 space with two trials, one for mild to moderate C-19 and one for severe to critical C-19. The latter is a phase 2b/3 390 patient trial with 11 centers listed, only 3 actively recruiting as I write. It's an interesting mAb targeting the well-know CCR5 T cell receptor, a genetic deficiency of which confers immunity to HIV without other apparent health problems. The company ran an EAP and boasted "remarkable" results saving the lives of 4 or 11 patients, 7 of whom were immunosuppressed organ transplant patients. They followed that up with a paper documenting reduction in RANTES (CCL5) and viral copies. They are recruiting critical patients, limiting patients to a P/F of 150 or higher, but accepting patients in shock or on ECMO, which is unusual. Yesterday they announced a third trial in Mexico. Management has come under criticism due to its handling of the BLA and some insider sales of stock. A company worth watching, all of their results need to be verified imo. Potential drawbacks of the molecule are liver, adverse interactions and ?increased risk of infection in this acute population. I find it MOST surprising that Pfizer (Maravoc, which targets the same receptor) has been very quiet on re-purposing to Covid-19. In any event, CYDY is definitely on my watch list, eventual synergies with rem-L cannot be ruled out.
6. Humanigen Lenzilumab The company has a market cap of just $100M. I mention it because they have a mAb directed at the same target as gimsilumab. Despite their small size they've managed FDA authorization for a full phase 3 trial with 238 patients. They have 9 centers participating including the most prestigious Mayo Clinic. They are targeting C-19 pneumonia just prior to intubation... bigger pool of potential patients, smaller recruitment size and the phase 3 means they could beat us to the finish line for FDA first-mover bragging rights - while we get to treat their failures. Ouch. Still, MoA has to be proven for all of these molecules that target only part of the storm problem... I think live cells will win at the end of the day. On my watch list.
7. Regeneron Sarilumab (Kevzara) The market cap is $64.2B. Another mAb, this one an IL-6 inhibitor being re-purposed from RA. So, the advantage is that it already has FDA approval for that indication. The company has deep pockets and has 63 medical centers enrolling. The trial started April 30 with an anticipated primary completion date in September. They are targeting pneumonitis patients with a primary endpoint of progression to ARDS/ventilator at 28 days. I think the mAb will prove weak for this indication, trials will tell. It has toxicities and carries black box warnings for serious infection and oppotunistic infection, not ideal for ICU patients. Still, on my watch list.
8. Roche/Genetech Tocizilumab (Actemra) Another anti-IL-6 mAb already approved for RA. This one also has approval for Cytokine Release Syndrome related to treatment with CAR-T cells. There was a report in the NEJM on May 12 reporting favorable experience using this molecule in China to treat 21 patients with C-19 lung illness. 15 of 21 had a decrease in O2 requirements. Genentech is pursuing this vigorously with 44 different trials registered phase 2 and phase 3 in multiple countries. So, very deep pockets... will they beat us to the finish line - or take other action if their molecule stumbles due to reasons I listed above? Trials will tell.
9 Celularity CYNK-001 I believe the company is private. Not really a competitor but I mention them briefly because they got some publicity a few weeks ago from Rudy Giuliani, the former Mayor of New York City who interviewed the CEO on his podcast. The company is developing Natural Killer cells, so a cell-based therapeutic that would not interact well with MSC's if given at the same time. They are targeting pre0intubation patients. So, a lot of publicity but it didn't get them too far with the FDA. They'll be doing and 86-patient trial at 5 different centers targeting patients not too sick with a PO2 above 95. And they'll be starting in phase 1.
10. Pluristem... not yet actively recruiting at this time.... I add them to the list just to round it out. They're number 3 in terms of cell based therapy, bogged down in phase 2 testing and dose finding as I mentioned before. I have grave doubts about administering 15 IM injections x 2 to unconscious ICU patients. But the FDA approved it, so let's see. Still waiting for a good explanation of how the cells will traverse hill and dale from the butt to the lungs in time to take action... their entry criteria are a bit looser, the only requirement is "ARDS".