Medivir – time for Blue-Sky-thinking2023-06-26 13:41
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There are talks about 10-bagger-shares but that is not enough - I would call Medivir a potential “double-digit-bagger” considering especially Fostrox but also many of the out-licensed products. This document focuses only on Fostrox. Almost two years ago I claimed that Medivir's Fostrox (at that time called MIV-818) could become "the holy grail" in liver cancer (HCC). Advances over time have been very positive, both in respect of market development and Fostrox development. An open phase 2a combination readout is due in 3 months or so, sometime in early fall. Insiders have been buying recently. Management is already expressing promising data as it is an open study. With good upcoming data “blue-sky thinking” is encouraged. Big Pharma is due to start moving around Medivir. Hence, from this level a double-digit-bagger is reasonable to assume.
To put it very short – Medivir has, with Fostrox - and its out-licensed portfolio - an excellent opportunity to become a very exciting and extraordinary investment.
Below you find:
-Short history of Medivir
-Treatment of primary liver cancer (HCC)
-Clinical studies and how they are measured
-Inflection points – dual and triple combinations
-Runway and coming major milestones
Medivir has a history of early research & development which today is licensed to pharma/biotechs globally. One product is in the market while at least three others are, probably from 2023, in early clinical development. Two phase 2 ready substances are open for licensing. These deals represent present and mainly future cash generation. This cash flow will support Medivir's own pipeline development where Fostrox is most clinically advanced.
Treatment of primary liver cancer (HCC)
Liver cancer is a difficult-to-treat cancer, no doubt.
In most cancers chemotherapy represent an effective way of treatment despite the development of immuno-oncology over past years. As a result of the systemic side effects chemo has not been possible to use in liver cancer. Instead, advanced liver cancer treatment has become an area where two classes of medicines usually are combined, Immuno-Oncology inhibitors and Kinase inhibitors. Global Data foresees a very strong growth in the liver cancer market, partly as a result of ever-increasing combination therapies (duals, triples) and the possibility to treat earlier than before. They forecast a market worth over 5 billion dollars in 2029. Liver cancer is the third/fourth deadliest cancer in the world, especially in the Eastern part of Asia and Africa but also steadily increasing in Europe & the US. Eastern Asia accounts for about 55% of all liver cancer. Globally about 800.000-850.000 new cases each year and the number of deaths is equally big.
Clinical studies and how they are measured
The Objective Rate of Response (ORR) is the first possible readout timewise in studies. The First Line in advanced HCC at present is a combo from Roche which reported an ORR of 27%, i.e. patients with complete/partial responses in relation to total number of patients in the study. It is somewhat tricky in HCC due to that sometimes also a modfiedORR (mORR) is reported which often is higher than the ORR. Comparing studies should not be done... but is always done. If done, it is important to also know which ORR measure is used.
The above Roche study showed a median Progression-Free-Survival (PFS) of 7 months, i.e. this cancer is getting worse rather fast. In a recent Roche triple combination phase 2 study the above combo was comparator and generated here only PFS of 4 months compared to the 7 months above. Most combo studies from the past years report PFS of median 3,5 months. As can be seen PFS in generally very low.
Clearly an alternative to the above combinations, with a new mechanism of action, is desired. This is where Fostrox comes into play, as a possible "holy grail" for liver cancer.
Fostrox is an ingenious liver directed chemotherapy. The oral molecule becomes active first in the liver and creates DNA damage to cancer cells without hurting normal cells, thus a local treatment. At first Medivir ran a good Phase 1a/1b mono trail with Fostrox. The present phase 1/2a study is run as a combination with Lenvima. Lenvima alone, a Kinase inhibitor, from Japanese Eisai (Bioarctic's Alzheimer partner) is today the prime second alternative (Second Line) after the Roche combo above.
Coming value inflection points for Fostrox/Lenvima - managing expectations
Already in September, i.e. in three months’ time, Medivir might be able to report tumor shrinkage data (ORR) from roughly 73% patients in the 2a combo study with Lenvima. In mid/end October the same for all patients including reasonable indications of forthcoming PFS data. Considering it is an open study with fast recruitment (very eager clinicians) AND very positive management comments in presentations recently, early data ought to be good. Another good indication is that chairman Hacksell, who has a very good pharma/bio network, also increased his investment recently.
Medivir's phase 2a combo study is naturally a small study, but it is in preparation for a larger phase 2b/3 combo study subject to that safety and efficacy data are reasonably good. If it reports an ORR of 20-30% it is very good. In mid/end October, if all, or almost all patients haven't progressed it will, as time goes by, most certainly also yield a favorable PFS (6+ months). With such data as per above, it might even be possible to get a "break-through designation" for a pivotal combo study which includes "Fast track" features such as accelerated approval.
Released, or otherwise communicated data to potential partners under NDA, can during the next 6 months very well be a trigger for an Asian license deal. In recent presentations this has been seen as a natural strategic step while Medivir will approach the US and European markets with its Orphan Drug designation, either on its own…. or also here in partnership. The other day Medivir got its Fostrox patent cleared in China. As management is saying in the press release, promising data and patents in most Asian countries now opens up for an Asian deal. The Asian market is by far the largest HCC market. Eisai is most probably one of the interested parties but could also be joined by other Japanese pharmas, as well as South Korean and Chinese pharma companies. Furthermore, global HCC players like Roche, AstraZeneca and Merck&Co have sizable Asian operations and could absolutely be willing to take on a license for Asia if that is up for grabs. An upfront in such a deal would probably amount to at least 40-60 musd - i.e. more than Medivir's current market cap.
Apart from the Fostrox&Lenvima combo in phase 2a Medivir also has combo data from phase 1a/b with Fostrox and Keytruda. That combo can be used later in e.g. a triple combination
Medivir released interesting pre-clinical data a few months ago at AACR regarding a triple combination.
https://www.medivir.com/investors/press-releases/2023/medivir-presents-new-data-at-aacr-showing-significantly-improved-antitumor-efficacy-in-non-clinical-tumor-models-with-fostrox-in-triple-combination . Roche has, as indicated above, recently released data for an own phase 2 triple consisting of the combo (Atezo+Beva) which now is standard of care in first line, plus an own antibody. Results were good but it is not unlikely that Roche, if Fostrox data are good, would like to run a triple Atezo+Beva+Fostrox to solidify its present Number One position. Furthermore, Astra Zeneca with the combo (Treme+Durva) has a second position to Roche in first line treatment - a position that is not that rich as patients that have tested the prime IO/TKI combo (the Roche combo), more often move to Lenvima (that was First line before the Roche combo arrived) instead of testing another similar IO/TKI combo. AstraZeneca would thus probably also like to test a triple with Fostrox. Several pharmas with other IO/TKI combos would probably also like enhance their effects in such a triple combo. Finally, and also very important, is Merck&Co/Eisai that to their big disappointment last year got good results for the Keytruda/Lenvima combo but missed the statistical significance. A triple with these two and Fostrox could be very valuable to Merck&Co/Eisai. Having several big pharmas with interest for Fostrox could, well handled, could prove to become a jackpot for Medivir.
Big Pharma is also moving to try treat in earlier stages (when at all being able to diagnose earlier) with their different combos. Several studies are being run in the intermediate stage before advanced liver cancer. In the medium term Fostrox may also prove to have a place in enhancing combos also here.
In the q1-23 report management noted that cash would take the company to q2-24. Considering the possibility to receive IGM milestones before that and the opportunities above from an Asia deal and/or one/several triple deals I would say Medivir is in a good financial position. A couple of other milestones could surface relating to Tango & SYB-China (Xerclear) but these are smaller, i.e. not rocking the financial position materially at the moment.
July- Aug Fostrox & Lenvima/Keytruda IND US
Sept-Oct Fostrox&Lenvima phase 2a top-line result
July-Dec Fostrox Asia license
March 24 Fostrox&Lenvima phase 2a full result
Q2 -24 Fostrox&Lenvima start phase 2b/3
July-Aug IGM cohort 5 ready
July-Aug Infex - IND - phase 1
July-Aug Tango -IND - phase 1
Sept IGM /start phase 1b
Oct-Dec SYB - Chinese approval of Xerclear
Jan-Jun 24 IGM possible milestone 15-30 musd
Anytime New licenses - Remetinostat & MIV-711
An example - If you invest e.g. a limited amount, say 20 tsek now, you can either:
Loose most or all of it – unlikely though
Get 100 tsek (5x) in 12-24 months
Get 300 tsek (15x) in 12-24 months
Get 500 tsek (25x) in 12-24 months
…or something in between. An exciting bet I would say!
I have followed Medivir for the last 5 years and know management and the BoD well. I am convinced of upcoming good data and deals, all resulting in a considerable value increase.
Medivir is one of my major life science holdings. Other major holdings are Calliditas, Bioarctic and Optomed in Finland. Major smaller holdings are Index Pharma & WNT Research.