Molecular Partners

Molecular Partners AG is a clinical-stage biopharmaceutical company based in Zürich, Switzerland. The company is developing a new class of potent, specific and versatile small-protein therapies called DARPins,[2] with potential clinical applications in a range of disease areas including oncology, immuno-oncology, ophthalmology, and immunology. Molecular Partners currently has two DARPin molecules in clinical development, and a broad pipeline of molecules in preclinical development.[1]

Molecular Partners AG
TypePublic
SIX: MOLN
IndustryBiotechnology
Founded2004
Headquarters
Schlieren, Zürich, Switzerland
Key people
William M. Burns, Chairman of the Board

Dr. Patrick Amstutz, Chief Executive Officer
Dr. Michael Stumpp, Chief Operating Officer
Andreas Emmenegger, Chief Financial Officer

Dr. Nicolas Leupin, Chief Medical Officer
Revenue29.1 million Swiss francs (CHF) (FY 2015)[1]
CHF -2.2 million (FY 2015)[1]
Total assetsCHF 194.0 million (Dec 31, 2015)[1]
Total equityCHF 151.8 million (Dec 31, 2015) [1]
Number of employees
89 FTE (Dec. 31, 2015) [1]
Websitewww.molecularpartners.com

History

Researchers at the University of Zürich, Switzerland formed Molecular Partners AG in 2004 while studying monoclonal antibodies. These scientists discovered and developed the DARPin technology and launched the company using this platform.[2]

Molecular Partners became a publicly traded company in November 2014, when it was listed on the SIX Swiss Exchange.[3][4]

As of 2018, Molecular Partners has two cancer assets currently going through clinical testing.[5]

DARPins

DARPins are genetically engineered antibody mimetic proteins typically exhibiting highly specific and high-affinity target protein binding.[2] They are derived from natural ankyrin repeat proteins. Repeat proteins are among the most common classes of binding proteins in nature, responsible for diverse functions such as cell signaling and receptor binding.[2] DARPins constitute a new class of potent, specific and versatile small-protein therapies, and are used as investigational tools in various therapeutic and diagnostic applications.[2]

The simplest format of a DARPin is the mono-DARPin, consisting of one DARPin domain with specificity for one target. The molecular mass of a mono-DARPin is about 15 to 20 kDa (kilodaltons), depending on the exact design.[6] Several mono-DARPins can be linked (genetically or chemically) to multi-DARPins, which then combine multiple activities in one therapy. This approach enables the design of medicines that can inhibit multiple disease-specific targets and may improve outcomes for patients living with cancer, ophthalmic diseases and other disorders.[2]

Currently, Molecular Partners has two DARPin molecules in clinical development and a broad pipeline of molecules in preclinical development.[1]

Areas of Focus

Molecular Partners is currently focusing its DARPin platform on the fields of oncology, immuno-oncology, ophthalmology, and immunology.[1]

Oncology

Molecular Partners’ lead candidate in oncology is MP0250,[7] a proprietary multi-DARPin designed to inhibit VEGF and hepatocyte growth factor (HGF). In a poster presentation at the 'AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics' in Boston, Mass. on Saturday, November 7, 2015, a team of independent researchers presented the first demonstration in patients of the potential role of DARPin-based therapy in oncology.[8] Data from the Phase I study demonstrated good tolerability, favorable pharmacokinetics, and sustained exposure over multiple applications of MP0250 in a preliminary analysis in patients with solid tumors.[9]

In January 2016, the company announced plans for a Phase II trial of MP0250, a multi-DARPin® drug candidate targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), in combination with bortezomib (Velcade®) and dexamethasone in patients with multiple myeloma (MM) who have developed resistance to at least two prior regimens (including bortezomib and an immunomodulatory drug).[10] The Phase II trial is expected to be initiated in the second half of 2016.[10]

In preclinical studies, MP0274, a proprietary multi-DARPin with broad anti-HER2 activity, has shown promising data in model of HER 2-positive breast cancer, including those with lower levels of HER2 expression.[11]

Molecular Partners agreed to pair MP0250 with Tagrisso in a phase I lung cancer trial, working with AstraZeneca on the EGFR-inhibiting candidates.[12]

Immuno-Oncology

In March 2016, the company announced its strategic plan to expand its immuno-oncology pipeline by naming the first two development programs. The first is for a multi-DARPin® that inhibits the programmed cell death protein 1 (PD-1, a validated immune checkpoint target) and VEGF-A, while also binding to human serum albumin.[13] This tri-functional DARPin® is designed to normalize the tumor vasculature by inhibiting VEGF and increasing tumor-penetration and intra-tumor expansion of effector T-cells.[13] Additionally, the DARPin® binding domain to serum albumin is expected to yield a long half-life and to allow for potentially increased tumor penetration.[13]

The second immuno-oncology program is for the development of a highly specific activator of T-cells in the tumor stroma. It binds to co-stimulatory agonists on the surface of T-cells without activating them when bound in circulation – only once the T-cells enter the tumor microenvironment, the agonist is clustered via the DARPin® having a second specificity for a densely expressed target in the stroma.[13] This selective activation of T-cells is typically not seen for antibodies as they tend to directly cluster agonists through their Fc part and clustering on widespread Fc-receptors.[13]

Ophthalmology

Molecular Partners’ most advanced clinical candidate is abicipar (AGN-150’998, MP0112), an anti-VEGF (vascular endothelial growth factor) DARPin in late-stage development, in partnership with Allergan, an Abbvie company.[14] In Phase 2b studies, abicipar was shown to provide equal or potentially higher vision gains with fewer injections in patients with wet AMD (wet age-related macular degeneration), compared to standard anti-VEGF treatment with ranibizumab (Lucentis).[11]

Currently, abicipar is being investigated in four different clinical trials. The first two are Phase 3 safety and efficacy studies in patients with wet AMD; the aim of these studies is to test the safety and efficacy of abicipar in patients with wet AMD.[14][15] Molecular Partners anticipates clinical read-outs from these studies in the summer of 2018.[16]

The third clinical trial is a Phase 2 safety and efficacy study in patients with wet AMD, designed to establish comparability between Japanese and non-Japanese patients.[17] The fourth study is a Phase 2 safety and efficacy of abicipar in patients with diabetic macular edema.[18]

Immunology

Molecular Partners is developing DARPins against several targets important for the treatment of inflammatory and auto-immune diseases. Its lead compound targets both IL-13 and IL-17 with long systemic half-life and potential use in pulmonary indications.[19]

Partnerships/Business Development

Molecular Partners has negotiated three agreements with Allergan to develop therapies for ophthalmology (including abicipar), one in 2011[20] and two in 2012.[21] In 2011, the company licensed its lead asset MP0112, now called abicipar, to Allergan.[20] In 2012, Molecular Partners and Allergan expanded their relationship by signing two separate new agreements to discover, develop, and commercialize proprietary therapeutic DARPin products for the treatment of serious ophthalmic diseases.[21]

In October 2020, as part of a joint venture to develop therapeutic drugs to combat COVID-19, the Swiss pharmaceutical giant Novartis bought 6% of all shares outstanding in Molecular Partners at 23CHF a share.[22]

References
  1. Molecular Partners AG Annual Report 2015 (PDF). March 2016.
  2. Plückthun, A (2015). "Designed ankyrin repeat proteins (DARPins): binding proteins for research, diagnostics, and therapy". Annu. Rev. Pharmacol. Toxicol. 55 (1): 489–511. doi:10.1146/annurev-pharmtox-010611-134654. PMID 25562645.
  3. Förster, Jan-Henrik (November 5, 2014). "Bloomberg". Bloomberg. Bloomberg. Retrieved September 29, 2016.
  4. "2014 Annual Report" (PDF). Molecular Partners. March 2015. Retrieved September 29, 2016.
  5. Taylor, Nick Paul (21 June 2018). "Molecular Partners names Regeneron cancer leader as CSO in reshuffle of leadership team". Fierce Biotech. Retrieved 26 June 2018.
  6. Binz, HK; Amstutz, P; Kohl, A; Stumpp, MT; Briand, C; Forrer, P; Grütter, MG; Plückthun, A (2004). "High-affinity binders selected from designed ankyrin repeat protein libraries". Nature Biotechnology. 22 (5): 575–582. doi:10.1038/nbt962. PMID 15097997.
  7. Binz, H. Kaspar; Stumpp, Michael T.; Forrer, Patrik; Amstutz, Patrick; Plückthun, Andreas (September 12, 2003). "Designing repeat proteins: well-expressed, soluble and stable proteins from combinatorial libraries of consensus ankyrin repeat proteins". Journal of Molecular Biology. 332 (2): 489–503. CiteSeerX 10.1.1.627.317. doi:10.1016/s0022-2836(03)00896-9. ISSN 0022-2836. PMID 12948497.
  8. "American Association for Cancer Research". November 2015. Retrieved September 29, 2016.
  9. "Preliminary Phase I Results Demonstrate Potential Utility of DARPins in Anticancer Treatment". November 7, 2015. Retrieved September 29, 2016 – via www.molecularpartners.com.
  10. "Molecular Partners to Conduct Phase II Trial of MP0250, a Multi-DARPin Targeting VEGF and HGF, in Multiple Myeloma". January 8, 2016. Retrieved September 29, 2016 – via www.molecularpartners.com.
  11. ""Molecular Partners Corporate Presentation" (PDF). September 2015.
  12. Taylor, Phil (11 April 2018). "Molecular Partners gets AZ support for lung cancer trial". Fierce Biotech. Retrieved 26 June 2018.
  13. "Molecular Partners Reveals Programs in Immuno-Oncology". March 7, 2016. Retrieved September 29, 2016 – via www.molecularpartners.com.
  14. "Clinical trial number NCT02181517 for A Safety and Efficacy Study of Abicipar Pegol in Patients With Neovascular Age-related Macular Degeneration". ClinicalTrials.gov.
  15. "Clinical trial number NCT02462928 for A Safety and Efficacy Study of Abicipar Pegol in Patients With Neovascular Age-related Macular Degeneration (CDER)". ClinicalTrials.gov.
  16. "MP Half-Year Report 2016" (PDF). Molecular Partners Investor Page. September 1, 2016. Retrieved September 29, 2016.
  17. Clinical trial number NCT02181504 for "A Study of Abicipar Pegol in Japanese Patients With Neovascular Age-related Macular Degeneration" at ClinicalTrials.gov.
  18. Clinical trial number NCT02186119 for "A Study of Abicipar Pegol in Patients With Diabetic Macular Edema" at ClinicalTrials.gov.
  19. "Molecular Partners regains rights to multi-DARPin® drug candidate targeting IL-13 & IL-17 for pulmonary indications from Janssen". Molecular Partners News Releases. October 6, 2016. Retrieved October 6, 2016.
  20. Allergan Licenses Molecular Partners’ Phase II Eye Disease Protein Therapeutic for $45M". Genetic Engineering and Biotechnology News. May 4, 2011.
  21. "Molecular Partners Gets $62.5M as Allergan Repeats on Darpins". Bioworld. August 21, 2012.
  22. Global Legal Chronicle Molecular Partners Option and License Agreement with Novartis (30 October 2020)
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