[U] Various Tea Leaves To Be Read -- On Merck's "Cancer Vaccines" Initiative -- In Moderna's IPO Prospectus

I will leave to another post the discussion of how richly Merck is being rewarded (at least on a paper-, not yet realized- investment gains basis), for its nearly $425 million in commitments to this storied unicorn. One of my several prior posts on this relationship may be found here. Suffice it to say for today that Mr. Frazier has once again proven himself a very savvy steward.

Even if the ultimate bio-science product(s) underwhelm, he has put Kenilworth in a nice position to liquidate, in an orderly fashion (i.e., profit from), the four years' worth of investments (into a deep trading market in Moderna that is nearly certain to develop) -- post IPO closing. Of course, Merck will only take that route if the payoffs, from the partnered mRNA candidates, begin to look less than likely, for multi-billion dollar launches, and steady commercialization.

So -- also for today -- as we return to our original power-alley, we would note that the mRNA approach Moderna uses is posting very promising albeit early results, in the same cancer patients Merck doses with its juggernaut Keytruda^®. And thus Mr. Frazier is already a double winner.

BTW, that alone ALSO means Martin Shkreli's jailhouse call -- to short Moderna -- will be a likely losing bet. We have revised our copy, over at that other property, now that we've digested the pre-IPO Moderna disclosures. [Motto: don't listen to convicted securities fraud felons, for bio-science investment advice.]

On then to the wonders that might unfold, should personalized cancer vaccines become a real probability. As the first step on that path, do read this bit -- which appears at page 200 of the Moderna IPO prospectus -- all as filed at the SEC's EDGAR window, overnight:

. . . .We [at Moderna] are collaborating with Merck to use the strength of our platform to develop cancer vaccines with multiple neoantigens unique to each patient, also known as personalized cancer vaccines, or PCVs.

Recent breakthroughs in cancer immunotherapy have demonstrated that powerful antitumor responses can be achieved by activating antigen specific T cells in a variety of cancer settings. Despite these advances, many patients still have incomplete or no response to anti-cancer therapies. One approach is to administer a cancer vaccine that encodes for peptides containing mutations found in their cancer, i.e., to create a personalized cancer vaccine composed of neoantigens unique to a patient’s tumor. Previous attempts have demonstrated the ability of mRNA and peptide-based platforms to drive immune responses toward patient-specific neoantigens. Preclinical studies have shown that the combination of cancer vaccines with checkpoint inhibitors provides improved benefit over single-agent therapies. Our platform is positioned for bringing personalized cancer vaccines to patients with our proprietary in silico design of each patient’s neoantigen-based mRNA vaccine, to be coupled with our automated cell-free manufacturing processes and infrastructure based in Norwood, MA, as well as our digital infrastructure. We believe these attributes coupled with our proprietary LNPs help differentiate our approach from ongoing efforts at developing mRNA-based cancer vaccines. mRNA-4157 is co-administered with pembrolizumab, marketed in the United States as KEYTRUDA. This is in collaboration with Merck as governed by a joint steering committee. NCI-4650 is a personalized cancer vaccine being tested by the National Cancer Institute, or NCI, as a monotherapy for patients with advanced, metastatic cancers. NCI-4650 only differs from mRNA-4157 in its neoantigen selection process. Both mRNA-4157 and NCI-4650 are in Phase 1 trials in the United States.

In Part A of the Phase 1 trial for mRNA-4157, as of November 15, 2018, 13 patients have been dosed with mRNA-4157 monotherapy of which 12 remain on study disease free post-operatively and one has relapsed. In Part B of the study, as of November 15, 2018, 11 patients have been dosed with mRNA-4157 of which 10 are in combination with pembrolizumab. For the 11 patients, there is one patient with a complete response prior to dosing with mRNA-4157, two patients with partial responses one of whom had failed prior checkpoint inhibitor therapy, three patients had stable disease, four patients progressed, and one patient was yet to be evaluated after starting treatment. As of November 9, 2018, we have interim immunogenicity data for 13 cancer patients and have detected potential antigen specific T cell responses in at least one patient. We have triggered planning for a randomized Phase 2 trial with Merck. . . .

[Updated @ 10 AM EST: other than to say I cannot fathom a situation where the CRISPR'd-babies abomination was medically prudent, or remotely ethical research, I'll likely have no additional comment on it. I leave it to the world's best scientists to excoriate the involved hack -- if he did actually even achieve it. End, update.]

All in all, we sense a renewed bounce in our step (with a visitor seen, elsewhere), given the return of clear skies, on a cold, but lustrously snow-whitened morning here.

नमस्ते