A D V E R T I S E M E N T F E A T U R E

A D V E R T I S E R R E TA I N S S O L E R E S P O N S I B I L I T Y F O R C O N T E N T

Medivirwww.medivir.com

Medivir—focusing on cancer one prodrug at a timeMedivir is developing tumor-directed nucleotide oral prodrugs to treat cancers with highly unmetmedical needs. The company’s lead drug candidate, MIV-818, is a liver cancer targeted prodrug thatMedivir is looking to develop alone in the USA and the EU and through partnerships elsewhere.

Swedish pharmaceutical company Medivir focuseson the development and commercializationof innovative treatments for cancers for whichexisting therapies are limited or missing. The com-pany’s therapeutic strategy consists of designingtumor-directed nucleotide prodrugs. Once takenup by the tumor cells, the nucleotide prodrugs arecleaved, and the nucleotides can efficiently disruptcell proliferation.

Medivir’s approach combines in-house clinicaldevelopment skills and industry experience thatallow the company to leverage knowledge andexperience from academic, health-care and globalindustrial partnerships.

Medivir’s lead asset is MIV-818, a liver-directed,oral nucleotide prodrug that has the potential to bean effective and well-tolerated treatment of livercancer. Hepatocellular carcinoma (HCC) is themost common form of primary liver cancer and thethird-leading cause of cancer-related deaths glob-ally. HCC is classified as an orphan disease in theEU and the USA, but exhibits a disproportionatelyhigh incidence in Asia. HCC’s orphan disease statusmay provide an opportunity to shorten the drugdevelopment lead time of MIV-818 through fasttrack designations from the European MedicinesAgency and the US Food and Drug Administrationand reaching cancer patients more rapidly.

“Our innovative prodrug approach could pro-vide benefit to patients worldwide,” said ChristinaHerder, EVP and COO of Medivir. “Through ourhighly collaborative approach, we aim to acceleratethe process of bringing these new medicines topatients in need.”

Targeting liver cancerHepatocellular carcinoma is counted among thedeadliest of cancers, with a 5-year survival rate ofjust 11%. HCC is genetically heterogeneous, makingit challenging to identify good molecular targets fortherapeutic intervention. Surgery is the only curativeoption, with all other systemic treatments—chemo-therapy, immunotherapy and radiotherapy—havinga mostly palliative effect. First-line therapies includesorafenib and lenvatinib, and second-line thera-pies consist mostly of a range of immuno-oncologydrugs approved in the USA.

The nucleoside analog troxacitabine has beenshown to have anticancer activity but develop-ment was suspended in 2008 owing to an insuf-ficient therapeutic window for this intravenousdrug candidate. Medivir has developed MIV-818,a prodrug which is cleaved inside the tumorcells to produce the active metabolite TRX-TP.Subsequently, TRX-TP is incorporated into DNA,

causing double-strand DNA breaks and cell death.MIV-818 also exhibits an enhanced antitumor effectin preclinical models of HCC when administered incombination with sorafenib.

In a clinical phase 1 study, clear signals of effect,measured as DNA damage observed in liver biop-sies from tumor tissue of patients treated withMIV-818, provided early proof of concept. Normalliver tissue did not appear to have been affected.

The clinical potential of MIV-818 includes its useas monotherapy and as add-on to standard-of-carefor treatment of liver cancer.

According to Herder, “our experience with MIV-818 will enable us to progress our candidate drug,MIV-828, into clinical development for hematologi-cal tumors next.”

Global outlookMedivir is building a solid pipeline of innovativecancer treatments by leveraging strategic partner-ships to accelerate the development of its new drugcandidates and reducing the time for them to reachpatients in need.

For MIV-818, Medivir is looking for a partner toco-develop and commercialize the compound inAsia. In particular, the company is looking for a

partner with proven clinical development experi-ence in key territories, e.g. China or Japan, up-to-date knowledge of local regulatory processes anda good commercial understanding of the Asianliver cancer market. Medivir also has a numberof other advanced clinical programs available forpartnering (Fig. 1).

As pointed out by Herder, “Medivir uses its inter-nal clinical development competence in combi-nation with geographic partnering to optimize itsability to move innovative compounds to the marketin key territories.”

Christina Herder, EVP & COOMedivirHuddinge, SwedenTel: +46 731 251 729Email: christina.herder@medivir.com

CON

TACT

Project Disease area Research Preclinical Phase 1 Phase 2 Phase 3 Market

Proprietary projects

MIV-818 Liver cancer

MIV-828 Blood cancer

Projects for licensing

Remetinostat MF-CTCL

BCC*

SCC*

Birinapant

MIV-711 OA

Outlicensed projects

Project Disease area Partner Preclinical Phase 1 Phase 2 Phase 3 Market

Xerclear Labial herpes GSK

MIV-802 Hepatitis C Ascletis (Greater China)

* Conducted by Stanford University** Conducted by NCI, USA

HNC (with radiation)**

Clinical phase

Fig.1 | Medivir’s pipeline includes already out-licensed projects, projects requiring licensing partnersand the latest generation of prodrug-based anticancer drugs: MIV-818 and MIV-828. HDAC, histonedeacetylase; MF, mycosis fungoides; SMAC, second mitochondrial-derived activator of caspases.

biopharmadealmakers.nature.com | March 2020 | B5