I've previously written about Moderna's phase 3 prospects (https://www.reddit.com/r/stocks/comments/1bkiv8o/moderna_mrna_to_paraphrase_its_not_about_covid/ ).
With this post I take a look at Moderna's mid-tier phase 2 pipeline. Stock analysts & by inference the market in general, more often than not ignore these products as they've become accustomed to Old Pharma's high failure rates, so it didn't make much sense to bother assessing / forecasting sales for such drugs. HOWEVER, it is my contention that as Moderna's platform has successfully managed to scale mRNA technology, while perhaps not (yet) a new paradigm, it arguably doesn't share to the same degree the failings of Old Pharma mid-tier drugs, as such I think it's phase 2 prospects should be treatment more favorably.
– Consider (27Mar24 Investor Event Presentation p134) Moderna's platform success versus the industry average…. Phase 1: Moderna 70% success V. Industry 35%, Phase 2: Moderna 78% success V. Industry 27%.
– Yeah, quite something, no wonder they & now me are crowing about it! [FYI: I've invested in Moderna & plan on doing so again in the future]
It is worth noting that all of the following programs are forecasted to have been launched by 2028
– This review ignores the phase 1 drugs that they've forecasted to be launched by 2028, Perhaps harshly, as Moderna often undertakes phase 1/2 studies that have generally larger study participant numbers hence stage 3 can come on fast (See below for proof of that!).
– I think it reasonable to assume that the progress of some of these phase 2 drugs indicates a launch prior to 2028, however I also imagine some could well be delayed &/or fail to launch. Similarly some not yet discovered drugs [i.e. 13Sep23 pod at5.25 We expect around 10 new drugs per year moving from the labs into development] could well have launched by 2028, however this is sheer conjecture.
- Flu 1020 & 1030, 1011 & 1012
POTENTIAL PATIENT POOL: The current flu market is c.$6bn, however could grow to c.$9bn in 2028. Worldwide 3-5M severe cases of influenza & 290-650K deaths annually.
KEY DATES: Unknown
COMPETITORS: mRNA 1020/30 was compared against Flublok….Primarily it’s Sanofi’s Fluzone, a currently licensed vaccine
A BRIEF OVERVIEW: As a reminder Phase 3 mRNA1010 met all its immunogenicity endpoints, it will form the foundation of a continuously improving influenza vaccine portfolio, with it focusing on WHO recommended quadrivalent (4 types) strains. With mRNA1020,1030 phase 1/2 study focusing on broader flu antigens (trialed against Flublok & mRNA1010, in a p101 study it produced similar Hemagglutination titers to both, but significantly more Neuraminidase titers than both. a 2fold increase of the latter has shown an c.30% reduction in infection) while a mRNA-1011,1012 Phase 1/2 study looks for an enhanced antigen selection, to tackle regional variations (no info yet).
2) Pediatric RSV 1345 (2-18yr)
POTENTIAL PATIENT POOL: A portion of the overall >$10bn market, estimated at c.$2-4bn for maternal & pediatrics.
KEY DATES: Interim data possibly in 2024.
COMPETITORS: I imagine it will be the regular RSV players, GSK (Arexvy) & Pfizer (Abrysvo).
A BRIEF OVERVIEW: On 27Mar24 Moderna said it initiated trials in the pediatric populations. No further info.
3) HSV: Herpes simplex virus; establishes life-long latent infections within sensory neurons, leading to genital herpes.
POTENTIAL PATIENT POOL: Globally, c.492m people have HSV-2, c.13% of the world’s population aged 15-49yrs.
KEY DATES: Unknown
COMPETITORS: There is currently no approved vaccine to treat HSV-2. Bexsero, a suppressive antiviral treatment, is the control in the Moderna study.
A BRIEF OVERVIEW: They are conducting a Phase 1/2 study of 300 healthy adults 18-55Yrs old with a history of HSV-2 infection >1Yr & 3-9 HSV genital recurrences in the prior 12Mths. They are looking at 3 dose levels, with a follow up 12Mths after study injection. It's HSV vaccine candidate it hopes will deliver a similar efficacy as Bexsero, with easier compliance with recommended therapy & associated quality of life would improve.
4) VZV: herpes zoster/shingles, causes painful and itchy lesions.
POTENTIAL PATIENT POOL: “Shingrix”, a competitor, 2022 sales of $4bn. Expected to grow to $5-6bn. It occurs in a 3rd of adults in their lifetime & incidence dramatically increases at >50yrs old.
KEY DATES: On 27Mar24 IT WAS MOVED TO PHASE 3. They're expecting additional results later this year, looking at the durability of antibodies & T cells.
COMPETITORS: Shingrix, an FDA approved drug with 90% efficacy!
A BRIEF OVERVIEW: The Phase 1/2 dose-ranging study enrolled 500 participants >50yrs old (& 35% >70Yrs old) & compared it head-to-head with Shingrix. It's the same antigen that's in Shingrix, so they can actually compare it against a licensed vaccine. It was a relatively large study designed to move it rapidly into phase 3; Released results.. [27Mar24 Pod] at 52.10 So, in summary, we listed comparable or higher CD4 & CD8 T cell responses as compared to Shingrix & was generally well tolerated across all dose levels we tested. We are advancing towards a pivotal Phase 3 trial.
5) EBV: Epstein-Barr virus; To prevent infectious mononucleosis, lymphomas, cancers & autoimmune diseases. Also a major Multiple sclerosis risk (>30x)
POTENTIAL PATIENT POOL: c.>1m US cases annually, with an c.95% EBV prevalence in the US & >160K deaths attributed to EBV-related malignancies. Globally, EBV-associated cancers account for over 200k new cases of cancer annually & 150k cancer deaths, representing c.1-2% of total global cancer incidence and cancer deaths.
KEY DATES: On 27Mar24 mRNA-1189 WAS MOVED TO PHASE 3.
COMPETITORS: There is currently no approved vaccine to prevent EBV.
A BRIEF OVERVIEW: They have two EBV vaccine candidates (mRNA-1195 for “MS & post-transplant lymphoproliferative disorder” & mRNA-1189 to prevent Infectious Mononucleosis). The mRNA-1195 study of 350 18-55yr old participants, enrolled Apr-Jul23 with a follow up after 6Mths designed to test 2 drug products at 4 different dose levels… And the mRNA-1189 was a phase 1(/2?), it codes for 4 antigens (i.e. 4 mRNA required), designed to test 4 different dose levels in c.270 participants 12-30Yrs old, with 27Mar24 results showing that at each timepoint, all dose levels delivered a measurable reduction in detectable EBV viral DNA at monthly intervals when compared to placebo. Although this was for a limited sample size, this impact continued at 6Mths & 1Yr after the last injection. It has been moved to a pivotal Phase 3 trial.
6) Norovirus: leading cause (18% of total) of diarrheal disease globally.
POTENTIAL PATIENT POOL: In the US 20m infections per year (globally 685m), 900 deaths (globally 200k) & 100k US hospitalizations. c.$2bn in US healthcare costs & lost productivity (c.$60bn worldwide); Global market estimate of $3-6bn.
KEY DATES: On 27Mar24 mRNA1403 WAS MOVED TO PHASE 3.
COMPETITORS: There is currently no approved vaccine.
A BRIEF OVERVIEW: Vaccine development has been challenging to date due to the broad & shifting diversity of genotypes which requires frequent vaccine updates. currently developing pentavalent (mRNA-1405) and trivalent (mRNA-1403). Both candidates are in a Phase 1(/2?) study in healthy adult participants 18-49yrs of age & 60-80yrs of age. In 664 participants enrolled & dosing was completed in Dec23. 27Mar24 interim results showed that a single dose of mRNA-1403 elicited a robust immune response across all dose levels. It has been moved to a pivotal Phase 3 trial.
7) Lyme: rash, fever, headaches, fatigue, joint pain swelling, stiffness & headaches for 6Mths or more.
POTENTIAL PATIENT POOL: 35,000 cases in the US & 85,000 in Europe per year.
KEY DATES: Unknown
COMPETITORS: There is currently no approved vaccine.
A BRIEF OVERVIEW: the FDA granted Fast Track Designation. This is Moderna's first attempt at a bacterial illness, which are very complex organisms relative to viruses. Both the seven-valent (mRNA-1975; addressing Lyme's biological complexity, designed to potentially offer broader strain coverage) & a single-valent (mRNA-1982) vaccines are in a Phase 1/2, with c.800 participants in the study. In both cases you take a vaccine before a bite, when bitten antibodies travel to the tick's gut killing the Borrelia bacteria!
8) Zika: An infected mosquitoes biting a pregnant woman can cause birth defects, although deaths are rare.
POTENTIAL PATIENT POOL: Can be huge. e.g. In French Polynesia (2015-16) 66% of the population was infected (c.183k) & millions infected in Brazil in 2015. It can result in lifelong care needs.
KEY DATES: Currently on hold, waiting for outside funding help.
COMPETITORS: There is no approved Zika vaccine.
A BRIEF OVERVIEW: A Phase 2 study (with BARDA), with c.800 participants was looking to evaluate the immunogenicity of two dose levels (1dose or 2dose schedule). This study is currently on hold, its been suggested this occurred when Moderna reallocated its finite resources to their programs.
When researching & then writing this post it really hammers home to me & hopefully to you, that Moderna's future doesn't have a great deal to do with Covid any more other than the c.$13bn in Covid cash that it will be spending on R&D etc.
For me a statement from its 27Mar24 press release really hit home (BB's comments in “[ ]”): “Moderna's vaccine portfolio targets large addressable markets, with an estimated total addressable market (TAM) of $52bn for Moderna infectious disease vaccines, which includes a respiratory vaccines TAM of more than $27 billion [Covid & RSV c.$10bn each & Flu $7bn] and a latent and other vaccines TAM of more than $25bn [By 2028 CMV $12bn, EBV $1.1bn, VZV $5.6bn, Norovirus $3-6bn].”
These number are huge. They will of course share some of that market with competitors (although Respiratory trial expenses are a serious barrier to entry!), but I reckon a lot of the Latent is pretty much Moderna's (at least initially) for the taking.
– Being conservative, lets assume these market projections are on the high side… Nonetheless, if you think that Moderna's total sales in their best years was 2021 $18.5bn & 2022 $19.3bn, were the share price was quite a bit higher, you'll get an idea why I invested in Moderna.
Also, Moderna is different company then, than now. Its manufacturing setup & new purpose built plants are anticipated, as sales rise, to significantly decrease their Cost of Sales (CoS). They've thrown around examples like $4bn in sales giving a 35% CoS, to $10bn sales giving 20%.
– But don't take my word for it…As Bancel himself said (27Mar24 “Vaccines and Business Updates” webcast).. at1hr46min “We use the same manufacturing for all of our products. Covid & Flu need seasonal updates, which is why our team is really busy in the spring / summer, because the window is very tight to supply the product on time. But in Q1, our facilities aren't very busy, so what if we could make [say] VZV product in Q1, say $1bn+ of it a year, then your incremental gross margin will be north of 90%“
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