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• EMPATHY global multi-center Phase 2 – 3 study, recruiting patients with COVID-19 infection, aiming to prevent worsening symptoms and hospitalization

• The study plans to enroll 2100 patients, with 400 patients to be enrolled into Phase 2, followed by 1700 patients in Phase 3

• Novartis has been granted an option from Molecular Partners to in-license global rights of ensovibep and MP0423 – DARPin® antiviral therapeutic candidates that are undergoing testing to target SARS-CoV-2 spike protein

• DARPin® therapeutics well suited for a pandemic setting due to multi-specific target binding, long half-life for sustained activity and highly scalable production, compared to monoclonal antibodies

Zurich-Schlieren, Switzerland, May 27, 2021. Molecular Partners AG (SIX: MOLN) and Novartis announced today the start of the clinical trial EMPATHY, a Phase 2 and 3 study, to explore the use of its novel DARPin® therapeutic candidate ensovibep (MP0420) for the treatment of COVID-19. Novartis will conduct the clinical trial program for ensovibep, with Molecular Partners as sponsor of the studies. In March 2021, Molecular Partners reported positive initial Phase 1 results in healthy volunteers.

The EMPATHY clinical trial program is investigating the safety and efficacy of ensovibep in patients with COVID-19, who are in the early stages of infection, to prevent worsening symptoms and hospitalization. The study will enroll 400 patients in Phase 2 to identify a dose with optimal safety and activity, with initial results anticipated in August 2021. At that point Phase 3 will move ahead with an additional 1,700 patients with results anticipated in H1 2022. If the initial EMPATHY trial results are convincing, this would pave the way for Novartis to seek expedited approval via the FDA’s Emergency Use Authorization (EUA).

Those eligible for the EMPATHY trial are adults, over the age of 18, with a positive SARS-CoV-2 antigen test and who are experiencing at least two pre-determined mild/moderate symptoms of COVID-19 within 7 days of their diagnosis.

“Novartis remains unwavering in our efforts to help combat COVID-19, including our support to deliver treatment options for patients around the globe,” said Dr. Lutz Hegemann, Group Head, Corporate Affairs and Global Health, Novartis. “Today, with Molecular Partners, we’re announcing an important next step in the development of ensovibep, which holds promise to respond to breakthrough disease and new variants in the future. We are hopeful the results of this clinical trial program will provide a reliable treatment option for patients with COVID-19.”

Novartis believes a multi-solution strategy is needed to overcome COVID-19, one that utilizes a range of diagnostic and therapeutic options, depending on the needs of individual patients. Every country should have access to effective medicines to treat COVID-19 and despite availability of vaccinations, there continues to be disease transmission and there is likely to continue to be breakthrough disease.

“By virtue of its tri-specific design, ensovibep was built to resist viral mutations and indeed shows potent inhibition of all variants of concern to date, with the potential to maintain activity also for future variants. This type of broad spectrum activity is essential for any treatment of relevance for patients with COVID-19,“ said Patrick Amstutz, Chief Executive Officer, Molecular Partners. “Reaching this important clinical milestone is not only a key step to combat this virus, but also validating our DARPin approach to generate multispecific antiviral therapies in the fight against global pandemics.”

Initial findings from the Phase 1 trial of ensovibep showed it to be safe and well tolerated with no significant adverse events. Predictable exposure was seen post-administration, confirming the expected half-life of two to three weeks. These data confirmed the systemic administration of a multi-specific DARPin® antiviral therapy to be safe and well tolerated and support plans for additional clinical work in patients diagnosed with COVID-19, as part of the EMPATHY trial. The preclinical work for MP0423 is still ongoing and is being led by Molecular Partners.

 

Sustained binding against new variants of Covid-19

Molecular Partners, in collaboration with academic and government partners, has conducted in vitro experiments using pseudovirion models of SARS-CoV-2 to analyze for infectivity in the presence of ensovibep. These models represent new variants first identified in UK (B1.1.7), South Africa (B.1.351), Brazil (P.1), California (B.1.429), New York (B.1.526), emerging variants R.1 and A.23.1, the individual key mutations of the variants identified in India, B.1.617 and B.1.618, and other key spike mutations identified to date. The results suggest ensovibep continues to retain full potency against the new viral variants of SARS-CoV-2, and could have the potential for sustained binding to additional COVID-19 variants, as they may appear in the future.

 

Ensovibep enrollment in ACTIV-3 trial

Molecular Partners and Novartis also recently announced the inclusion of ensovibep in the NIH-Sponsored ACTIV-3 Trial (National Institute of Health’s (NIH) Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program) that aims to prioritize and push forward development of the most promising COVID-19 therapies. ACTIV-3 is a global Phase 3 trial that will investigate the safety and efficacy of ensovibep in adults hospitalized with COVID-19, with an aim to enroll up to 1,000 patients. The first patient dose is expected to be administered in June 2021, with an interim analysis after 300 patients with mild-to-moderate disease. These patients will receive either ensovibep or a placebo. Trial participants will also receive an existing standard of care for COVID-19, including the FDA-approved antiviral remdesivir. If the treatment has a positive risk-benefit profile, the study will enroll an additional 700 patients for further testing. Ensovibep is the first non-antibody therapy assessed in ACTIV-3, supporting a different approach for COVID-19 treatment.

 

The collaboration with Novartis

Molecular Partners is proud to be collaborating with Novartis to develop two DARPin® therapies designed for potential use against COVID-19, ensovibep and MP0423, with an option for Novartis to in-license global rights from Molecular Partners and development responsibilities to both therapies. Novartis will also be responsible for manufacturing, distribution and commercialization of both therapies.

The development program will be led by Molecular Partners until Phase 1 is complete and will be handed over to Novartis to conduct the pivotal clinical trial EMPATHY, with Phase 2 and 3 trials, with Molecular Partners as sponsor of these trials. Molecular Partners will perform all remaining preclinical work for MP0423.

 

About Molecular Partners AG

Molecular Partners AG is a clinical-stage biotech company developing DARPin® therapeutics, a new class of custom-built protein drugs designed to address challenges current modalities cannot. The Company has formed partnerships with leading pharmaceutical companies to advance DARPin® therapeutics in the areas of ophthalmology, oncology and infectious disease, and has compounds in various stages of clinical and preclinical development across multiple therapeutic areas.

 

For further details, please contact:

Investors:
Seth Lewis
seth.lewis@molecularpartners.com
Tel: +1 781 420 2361

Media:
Shai Biran, Ph.D.
shai.biran@molecularpartners.com
Tel: +1 978 254 6286

Thomas Schneckenburger, European IR & Media
thomas.schneckenburger@molecularpartners.com
Tel: +41 79 407 9952

 

Forward-looking statements

This press release may contain certain forward-looking statements relating to the company and its business. Although the company believes its expectations are based on reasonable assumptions, all statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the company’s control. These statements may include, without limitation, any statements preceded by, followed by, or including words such as “target,” “believe,” “expect,” “aim,” “intend,” “may,” “anticipate,” “estimate,” “plan,” “project,” “will,” “can have,” “likely,” “should,” “would,” “could”, and other words and terms of similar meaning or the negative thereof. Forward-looking statements involve certain risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of the company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. Except as required by law, the company assumes no obligation to update any such forward-looking statements, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.

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• in vitro studies show ensovibep (MP0420) maintains full potency against the known mutations of SARS-CoV-2, including those present in variants first identified in Brazil, California, India, and New York, in addition to the previously reported variants originating from the UK and South Africa

• Ongoing Phase 2 pilot study of ensovibep in ambulatory patients now expanding into second cohort

• Two global Phase 2 and 3 clinical studies of ensovibep on track for initiation this month

Zurich-Schlieren, Switzerland, May 06, 2021. Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin® therapeutics, today announced results from parallel laboratory studies conducted in collaboration with academic and government partners in Switzerland and the United States. The studies assessed the inhibition of new viral variants by leading SARS-CoV-2 anti-infective molecules, including ensovibep and MP0423. New variants are often associated with faster transmissibility and a potential ability to evade the currently available monoclonal antibodies and the immunity induced by some vaccines. On top of the previously reported inhibition of the variants first identified in the UK and South Africa, the new results reported today show that ensovibep continues to retain full potency against the new viral variants of SARS-CoV-2, including the variants first identified in Brazil, California, and New York as well as the key mutations in the Indian variant.

“By designing ensovibep to target the viral spike protein in three different places, we aimed to create a candidate capable of achieving high potency while retaining efficacy as the virus mutated. These new results show that ensovibep remains, as designed, fully potent against the emerging variants of SARS-CoV-2, which have received increasing attention as our understanding of COVID-19 shifts to regarding it as a chronic, evolving global health concern,” said Patrick Amstutz, Ph.D., chief executive officer of Molecular Partners. “These data are encouraging as we and our partners at Novartis prepare to enter two major clinical trials: EMPATHY in ambulatory patients and the NIH-sponsored ACTIV-3 in hospitalized patients. We are hopeful that these data will translate into patient benefits for those who are potentially infected with these same variants.”

The study design and results will be updated on the research preprint service bioRxiv here. This research builds upon prior analysis of the UK and South African strains, where ensovibep demonstrated full activity, and potential superiority compared to monoclonal antibodies currently being investigated as antiviral cocktails.

In the study update, based on two pseudovirion models, new SARS-CoV-2 variants first identified in Brazil P.1 (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F), California B.1.429 (S13I, P26S, W152C, L452R, D614G), New York B.1.526 (L5F, T95I, D253G, E484K, D614G, A701V) as well as emerging variants R.1 (W152L, E484K, D624G, G769V) and A.23.1 (F157L, V367F, Q613H, D614G, P681R) and the individual key mutations of the variants identified in India, B.1.617 and B.1.618, were analyzed for infectivity in the presence of different inhibitors. Ensovibep was shown to strongly neutralize these variants, as well as variants created to harbor multiple individual key point mutations in SARS-CoV-2. While maintaining inhibitory activity, MP0423, the Company’s second COVID-19 candidate, has shown reduced protection against some of the variants. Specifically, mutations in the N-terminal domain were identified to be the key contributors to some reduction of potency. Further analyses in context of the full lineages B.1.617 and B.1.618, first described in India, are ongoing. Full data can be found in the updated bioRxiv publication linked above.

Molecular Partners’ lead anti-COVID-19 therapeutic candidate, ensovibep, has been administered to healthy subjects in the Company’s Phase 1 trial, with initial results showing it to be well-tolerated, with a half-life in the range of 2-3 weeks. Additionally, a single-arm Phase 2 trial with ensovibep in COVID-19 ambulatory patients was initiated in March 2021 at a single center in the Netherlands. The initial Phase 1 results have informed the decision to move forward with the EMPATHY clinical trial program, which is being conducted by our partner Novartis, with Molecular Partners as sponsor. The EMPATHY trial is a global, multi-center Phase 2 and 3 study that will seek to enroll 2,100 patients with COVID-19 in the ambulatory setting, to evaluate the safety and efficacy of ensovibep in preventing worsening symptoms and hospitalizations. In parallel, ensovibep will also be tested in hospitalized COVID-19 patients, in a new sub-trial of the National Institutes of Health’s (NIH) Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-3) Program Phase 3 clinical trial.

 

About Molecular Partners AG

Molecular Partners AG is a clinical-stage biotech company developing DARPin® therapeutics, a new class of custom-built protein drugs designed to address challenges current modalities cannot. The Company has formed partnerships with leading pharmaceutical companies to advance DARPin® therapeutics in the areas of ophthalmology, oncology and infectious disease, and has compounds in various stages of clinical and preclinical development across multiple therapeutic areas.

 

For further details, please contact:

Investors:
Seth Lewis
seth.lewis@molecularpartners.com
Tel: +1 781 420 2361

Media:
Shai Biran, Ph.D.
shai.biran@molecularpartners.com
Tel: +1 978 254 6286

Thomas Schneckenburger, European IR & Media
thomas.schneckenburger@molecularpartners.com
Tel: +41 79 407 9952

 

Forward-looking statements

This press release may contain certain forward-looking statements relating to the company and its business. Although the company believes its expectations are based on reasonable assumptions, all statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the company’s control. These statements may include, without limitation, any statements preceded by, followed by, or including words such as “target,” “believe,” “expect,” “aim,” “intend,” “may,” “anticipate,” “estimate,” “plan,” “project,” “will,” “can have,” “likely,” “should,” “would,” “could”, and other words and terms of similar meaning or the negative thereof. Forward-looking statements involve certain risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of the company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. Except as required by law, the company assumes no obligation to update any such forward-looking statements, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.

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Zurich-Schlieren, Switzerland, May 04, 2021. Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin® therapeutics, announced today its interim management statement for the period ending March 31, 2021.

“Molecular Partners continues to grow and expand the reach of our DARPin® therapeutics platform, with the COVID-19 pandemic forming a meaningful change agent for us,” said Patrick Amstutz, Ph.D., chief executive officer of Molecular Partners. “Twelve months ago, we were only at the initiating stages of our COVID-19 program, while this year we are approaching Phase 3 clinical trials with our partners at Novartis. I am extremely proud of our team and partners for not only bringing us to this stage of development in our new antiviral program, but also for continuing to advance our targeted oncology pipeline.”

 

Research & Development Highlights

• COVID-19 antiviral programs:
  • Completed Phase 1 dosing of ensovibep (MP0420) across three dose cohorts, and announced initial positive results
  • Published data showing that ensovibep is effective in vitro against all variants of concern analyzed
  • Initiated single-arm Phase 2 study of ensovibep in COVID-19 positive patients, in the ambulatory setting
  • A global Phase 2 – 3 study in ambulatory patients in collaboration with Novartis initiating enrollment in May 2021

• AMG 506 (MP0310) in solid tumors:
  • Proof of mechanism of action achieved, showing dose-dependent tumor accumulation and local activation of immune cells, as demonstrated after the first dose
  • Clinical studies ongoing to establish optimal dose regimen and activity with weekly dosing
• MP0317 (FAP X CD40):
  • Investigational New Drug Application (IND)-enabling work near completion
  • Expected to enter the clinic in the second half of 2021
• Four scientific posters published recently at the 2021 American Academy for Cancer Research (AACR) Annual Meeting, virtually from April 10-15:
  • Initial results highlighting the Company’s new AML focused multi-specific T-cell engager program
  • Additional data presented for MP0317, CD3 T cell engagers, and peptide-MHC DARPin® programs

 

Operational and financial highlights:

• Election of two new members to the Company’s Board of Directors: Agnete Fredriksen, Ph.D., and Dominik Höchli, M.D.
• Strong financial position with CHF 145.6 million in cash (incl. short term deposits) as of
  March 31, 2021
• Net cash used in operating activities of CHF 29.9 million in Q1 2021
• Operating loss of CHF 18.5 million and net loss of CHF 16.6 million in Q1 2021
• Company funded into 2023, excluding any potential payments from R&D partnerships

 

Clinical Updates:

COVID-19 program advancing in the clinic

Molecular Partners’ lead anti-COVID-19 therapeutic candidate, ensovibep (MP0420), has been administered to healthy subjects in the Company’s Phase 1 trial, with initial results showing it to be safe and well-tolerated, with a half-life in the range of 2-3 weeks. Additionally, a single-arm Phase 2 trial with ensovibep in COVID-19 ambulatory patients was initiated in March 2021 at a single center in the Netherlands. The initial Phase 1 results have informed the decision to move forward with the EMPATHY clinical trial program in April 2021, which is being conducted by our partner Novartis, with Molecular Partners as sponsor. The EMPATHY trial is a global, multi-center Phase 2 and 3 study that will seek to enroll 2,100 patients with COVID-19 in the ambulatory setting, to evaluate the safety and efficacy of ensovibep in preventing worsening symptoms and hospitalizations. In parallel, ensovibep will also be tested in hospitalized COVID-19 patients, in a new sub-trial of the National Institutes of Health’s (NIH) Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-3) Program Phase 3 clinical trial.

In addition to the clinical development, ensovibep continues to be tested in vitro for its inhibition of infectivity in newly discovered variants of the virus. To date, ensovibep has been shown to be effective in inhibiting viral infectivity in all variants and point mutations of concern.

Phase 1 trial of AMG 506 (MP0310) (FAP X 4-1BB)

As presented in December 2020 at our R&D day, preliminary clinical data from the ongoing Phase 1 clinical trial of AMG 506 (MP0310) show that the molecule performs as intended. AMG 506 (MP0310) showed colocalization with FAP at low concentrations, and the FAP binding was observed to be dose dependent, with a saturation of the tumor-expressed FAP in high AMG 506 (MP0310) concentrations. Furthermore, by analyzing paired biopsies of patients, significant tumor-localized increases in immune activation were seen across multiple immune cell types after a single injection, while systemic inflammatory markers were unchanged, and no AMG 506 (MP0310) activity was seen in peripheral tissues.

Additional dosing work is ongoing in the current Phase 1 clinical trial to test dosing regimens, including the exploration of weekly dosing, aiming to identify the right dose to provide durable activity after several injections of our tumor localized 4-1BB agonist.

MP0317 (FAP x CD40) IND-enabling work complete, scheduled to enter the clinic in H2 2021

In April 2021, Molecular Partners presented data from the MP0317 program at the AACR conference, showing new mechanism of action (MOA) data on the tumor-localized immune agonist MP0317, the second DARPin® protein in the Company’s immuno-oncology pipeline. As previously indicated, the company anticipates entering the clinic with MP0317 on the second half of 2021.

First CD3 T cell engager program to focus on AML therapies

As recently presented at the AACR conference, Molecular Partners’ first CD3 T cell engager will be focused on targeting AML tumor cells as well as T cells, to activate the immune cells against the tumor. Initial proof of concept data shows the Company was able to achieve a wide therapeutic window using a triple- tumor-antigen targeting CD3 DARPin® engager molecule.

 

Balance sheet: Strong cash and equity positions as of March 2021

Molecular Partners’ financial performance for the first three months of 2021 reflects an operating cash outflow of CHF 29.9 million. Cash and short-term deposits decreased by CHF 28.1 million in Q1 2021 to CHF 145.6 million as of March 31, 2021 (year-end 2020: CHF 173.7 million). The decrease in cash and short-term deposits was driven by a large prepayment of CHF 9.3 million for the manufacturing of commercial supply for ensovibep.

As of March 31, 2021, the company employed 151.6 FTEs, a 9% increase year-over-year, with approximately 82% of employees serving in R&D functions.

 

Financial outlook 2021

For the FY 2021, at constant exchange rates, the company continues to expect total expenses of CHF 65-75 million, of which around CHF 6 million will be non-cash effective costs.

In terms of cash outflow the company expects a gross cash utilization of CHF 85-95 million for FY2021, which includes a total of CHF 20 million payable to Novartis for the manufacturing of commercial supply (of which CHF 9.3 million occurred during Q1 2021). This cash flow guidance does not include any potential receipts from R&D partnerships.

With CHF 145.6 million cash at hand and no debt as per March 31, 2021 the company expects to be funded into 2023, excluding any potential receipts from R&D partners.

 

Financial Calendar

26 August 2021                    Publication of Half-year Results 2021 (unaudited)

28 October 2021                  Interim Management Statement Q3 2021

 

About DARPin® therapeutics

DARPin® therapeutics are a new class of custom-built protein therapeutics based on natural binding proteins that open a new dimension of multi-functionality and multi-target specificity in drug design. A single DARPin® candidate can engage more than five targets, and its flexible architecture and small size offer benefits over conventional monoclonal antibodies or other currently available protein therapeutics. DARPin® therapeutics have been clinically validated through to registration via the development of abicipar, Molecular Partners’ most advanced DARPin® drug candidate. The DARPin® platform is a fast and cost-effective drug discovery engine, producing drug candidates with optimized properties for development and very high production yields. DARPin® is a registered trademark owned by Molecular Partners AG.

 

About Molecular Partners AG

Molecular Partners AG is a clinical-stage biotech company developing DARPin® therapeutics, a new class of custom-built protein drugs designed to address challenges current modalities cannot. The Company has formed partnerships with leading pharmaceutical companies to advance DARPin® therapeutics in the areas of ophthalmology, oncology and infectious disease, and has compounds in various stages of clinical and preclinical development across multiple therapeutic areas.

 

For further details, please contact:

Investors:
Seth Lewis
seth.lewis@molecularpartners.com
Tel: +1 781 420 2361

Media:
Shai Biran, Ph.D.
shai.biran@molecularpartners.com
Tel: +1 978 254 6286

Thomas Schneckenburger, European IR & Media
thomas.schneckenburger@molecularpartners.com
Tel: +41 79 407 9952

 

Forward-looking statements

This press release may contain certain forward-looking statements relating to the company and its business. Although the company believes its expectations are based on reasonable assumptions, all statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the company’s control. These statements may include, without limitation, any statements preceded by, followed by, or including words such as “target,” “believe,” “expect,” “aim,” “intend,” “may,” “anticipate,” “estimate,” “plan,” “project,” “will,” “can have,” “likely,” “should,” “would,” “could”, and other words and terms of similar meaning or the negative thereof. Forward-looking statements involve certain risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of the company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. Except as required by law, the company assumes no obligation to update any such forward-looking statements, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.