Molecular Partners to Present Preclinical Data from MP0317, AMG 506 / MP0310 and Peptide-MHC Programs at AACR Annual Meeting

Molecular Partners to Present Preclinical Data from MP0317, AMG 506 / MP0310 and Peptide-MHC Programs at AACR Annual Meeting

Zurich-Schlieren, Switzerland, May 15, 2020. Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company that is developing a new class of custom-built protein therapeutics known as DARPin® therapeutics, today announced the presentation of preclinical data from three of the company’s programs at the American Academy for Cancer Research (AACR) Virtual Annual Meeting II, June 22-24, 2020.

Data to be presented on MP0317 (FAP x CD40) include in vitro and in vivo experiments which show that MP0317 displays significant tumor-localized immune activation without systemic toxicity seen with anti-CD40 antibody administration. In human B cells and dendritic cells, MP0317 was found to activate the CD40 pathway solely in the presence of fibroblast activation protein (FAP)-positive cells, confirming its strict dependence on FAP-mediated crosslinking. In a mouse model, a mouse-specific FAP x CD40 DARPin® molecule was found to substantially inhibit the progression of FAP-positive tumors without showing any of the toxicities seen with administration of a mouse CD40 antibody. FAP is a tumor-associated antigen abundantly expressed in many solid tumors, which Molecular Partners is leveraging to co-locate MP0317 to its target tissues.

Data to be presented on the peptide-MHC DARPin® program review the creation of bispecific DARPin® T cell engager proteins that bind with high specificity to a HLA-A2: SLL peptide-MHC complex. The constructed DARPin® proteins were observed to effectively activate T cells at a range of concentrations and to carry out highly targeted cell killing exclusively on those cells that were positive for NY-ESO-1, from which the SLL peptide is derived. This demonstrates proof-of-concept for the ability of DARPin® therapeutics to effectively drug peptide-MHC complexes.

Thirdly, a poster to be presented on AMG 506 / MP0310 (FAP x 4-1BB) describes pharmacokinetic and pharmacodynamic research to establish the optimal dose range for this novel tumor-localized immune agonist. AMG 506 / MP0310 is now in a Phase 1 clinical study.

The details are as follows:

  • MP0317: An oral presentation of MP0317 titled “A tumor-targeted CD40 agonistic DARPin® molecule leading to antitumor activity with limited systemic toxicity” will take place during the minisymposium entitled “Immunomodulatory Agents and Interventions” and will be accessible here.
  • Peptide-MHC DARPin®: “Application of the DARPin® technology for specific targeting of tumor-associated MHC class I: peptide complexes”, Poster No. 690
  • AMG 506 / MP0310: “Selection of first-in-human clinical dose range for the tumor-targeted 4-1BB agonist MP0310 (AMG 506) using a pharmacokinetic/pharmacodynamics modeling approach”, Poster No. 2273

Following their presentation, the posters will be made available on the corresponding section of the Molecular Partners website.

Financial Calendar

August 26, 2020 Publication of Half-year Results 2020 (unaudited)
October 29, 2020 Interim Management Statement Q3 2020

http://investors.molecularpartners.com/financial-calendar-and-events/

About DARPin® Therapeutics

DARPin® therapeutics are a new class of custom-built protein therapeutics based on natural ankyrin repeat 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 within a single molecule, 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 a new class of custom-built proteins known as DARPin® therapeutics, designed to address challenges current modalities cannot. The company has compounds in various stages of clinical and preclinical development with a focus on oncology. Molecular Partners has formed partnerships with leading pharmaceutical companies to advance DARPin® therapeutics across multiple therapeutic areas.

For more information regarding Molecular Partners AG, go to: www.molecularpartners.com.

For further details, please contact:

Seth Lewis, SVP IR, Comms, & Strategy
seth.lewis@molecularpartners.com
Tel: +1 781 420 2361

Tom Donovan, U.S. Media
tom@tenbridgecommunications.com
Tel: +1 857 559 3397

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

Disclaimer

This communication does not constitute an offer or invitation to subscribe for or purchase any securities of Molecular Partners AG. This publication may contain certain forward-looking statements and assessments or intentions concerning the company and its business. Such 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 reliance on these statements, particularly not in connection with any contract or investment decision. The company disclaims any obligation to update these forward-looking statements, assessments or intentions.

Molecular Partners Confirms Ultra-Potent Inhibition of SARS-CoV-2 Live Virus by Anti-COVID-19 DARPin® Candidates

  • DARPin® antiviral candidates demonstrate low picomolar potency in live virus assay
  • Candidate construction complete; two candidates ready for preclinical development & manufacturing
  • Therapeutic profile of a highly potent antiviral biologic with a long half-life supports both a prophylactic and therapeutic approach
  • Initiation of clinical studies planned for H2 2020

Zurich-Schlieren, Switzerland, May 7, 2020. Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company that is developing a new class of custom-built protein therapeutics known as DARPin® therapeutics, today announced completion of in vitro potency assessments of its DARPin® candidates targeting live, replicating coronavirus SARS-CoV-2. These candidates show extremely robust antiviral activity, with several candidates demonstrating complete neutralization with low picomolar potency. This suggests only very small amounts of these candidates may be required for therapeutic effect, which complements the company’s ability to rapidly manufacture DARPin® candidates with high yields.

“We are greatly encouraged by the emerging therapeutic profile of our program, that we believe suits the needs of this global pandemic. Our thanks to our colleagues at the Spiez Laboratory for working with us in testing our candidates against the live virus. Given the potency we see from these candidates, combined with characteristics of DARPin® therapeutics such as their manufacturability, low immunogenicity and shelf-stability, we are confident in moving to the next phase of work,” said Patrick Amstutz, Chief Executive Officer of Molecular Partners. “We continue to progress this program at high speed and expect to select a clinical candidate in the coming weeks, while we advance our plans for large-scale GMP manufacturing.”

The DARPin® candidates are half-life-extended and contain three distinct monomer DARPin® proteins that can simultaneously target the virus in different key areas, leading to cooperative binding and contributing to the extremely high potency now seen in vitro. The approach also allows neutralization of the virus via multiple mechanisms. Another significant advantage of a multi-specific antiviral is its potential ability to protect against viral ‘escape’, whereby a virus may develop resistance to any one antiviral mechanism.

The anti-COVID-19 candidates have subsequently been tested against the live virus, with assistance from the Spiez Laboratory, a division of the Swiss Federal Office for Civil Protection. In the completed in vitro potency assessments, dose-response assays with live, infectious SARS-CoV-2 virus showed that the selected candidates had an effective concentration for 50% inhibition (EC50) of less than 100 picomolar (pM) and completely inhibited infectious SARS-CoV-2 virion replication at low triple-digit pM concentrations.

“The DARPin® candidates show potent ant-viral activity against SARS-CoV-2 in our in vitro assay at Spiez Lab. We are looking forward to continue working with the Molecular Partners team on this project,” said Dr. Olivier Engler , Head of Virology at Spiez Laboratory.

From these tests, two candidates have been identified and will now move into in vivo studies, which will begin in May 2020. In parallel, GMP manufacturing is being secured, and the company is preparing for initiation of clinical studies in H2 2020.

About Molecular Partners’ anti-COVID-19 program

Molecular Partners is advancing antiviral DARPin® candidates with strong binding and neutralizing qualities against multiple epitopes on the SARS-CoV-2 spike protein that are crucial for infection. The company’s selection of a multi-specific DARPin® lead candidate will be based on its capability to perform three distinct mechanisms of action: blocking binding of the human ACE2 receptor, the virus’s primary docking mechanism to host cells; blocking binding of a specific protease essential for spike protein activation; and “handcuffing” the spike protein, preventing the conformational change it undergoes prior to injection of viral RNA into the human cell. One advantage of a multi-specific antiviral is its potential ability to protect against viral ‘escape’, whereby a virus may develop resistance to any one antiviral mechanism. The final candidate is also expected to have its half-life enhanced with a DARPin® domain that binds to human serum albumin (HSA) to support long-acting activity.

The construction of multi-specific candidates from monospecific proteins is the foundation of Molecular Partners’ drug discovery engine, and has yielded multiple clinical candidates in other indications.

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 a new class of custom-built proteins known as DARPin® therapeutics, designed to address challenges current modalities cannot. The company has compounds in various stages of clinical and preclinical development with a focus on oncology. Molecular Partners has formed partnerships with leading pharmaceutical companies to advance DARPin® therapeutics across multiple therapeutic areas.

For more information regarding Molecular Partners AG, go to: www.molecularpartners.com.

For further details, please contact:

Seth Lewis, SVP IR, Comms, & Strategy
seth.lewis@molecularpartners.com
Tel: +1 781 420 2361

Tom Donovan, U.S. Media
tom@tenbridgecommunications.com
Tel: +1 857 559 3397

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

Disclaimer

This communication does not constitute an offer or invitation to subscribe for or purchase any securities of Molecular Partners AG. This publication may contain certain forward-looking statements and assessments or intentions concerning the company and its business. Such 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 reliance on these statements, particularly not in connection with any contract or investment decision. The company disclaims any obligation to update these forward-looking statements, assessments or intentions.

Interim Management Statement Q1 2020: Continued progress on Abicipar, sharpened focus on pipeline activities

Research & Development Highlights:

  • Abicipar in neovascular wet age-related macular degeneration (nAMD):
    • Presentation of MAPLE data at the 2020 Angiogenesis, Exudation, and Degeneration symposium showed lower rates of intra-ocular inflammation than the rate observed in Phase 3 studies, as well as no incidences of retinal vasculitis
    • In March, a filing for approval of abicipar in nAMD was submitted to the Japanese Pharmaceuticals and Medical Devices Agency
    • In March, a manuscript detailing the pooled phase 3 data of abicipar was accepted for publication by Ophthalmology, the journal of the American Academy of Ophthalmology
  • MP0250 in multiple myeloma:
    • Discussions regarding potential collaborations for MP0250 are ongoing
    • As of April 30th, 2020, thirty patients have been enrolled at the 8mg/kg cohort in its ongoing study MP0250-201. 5/30 patients still receiving treatment will be monitored and treated, per protocol. The company will not enroll additional patients in this study.
  • AMG 506 (MP0310) in solid tumors:
    • Dose escalation ongoing with continued strong recruitment
    • Data from the dose escalation cohorts will be used to inform potential Ph1b combination studies with Amgen assets and will be conducted by Amgen
  • MP0317 (FAP X CD40):
    • United States Food and Drug Administration (FDA) Investigational New Drug Application (IND)-enabling work continues to progress
    • IND filing anticipated around the end of 2020
  • Three scientific posters accepted for 2020 American Academy for Cancer Research (AACR) Annual Meeting, to be held virtually from June 22-24
    • Topics will cover AMG 506, MP0317, and peptide-MHC DARPin® programs
  • In April, the company announced its efforts to design a highly potent DARPin® antiviral therapeutic against SARS-CoV-2, with candidate selection ongoing, and the potential to initiate clinical studies in H2 2020

Operational & Financial Highlights:

  • Election of three new members to our Board of Directors, including Sandip Kapadia, Vito Palombella Ph.D., and Michael Vasconcelles, M.D.
  • Cash and short-term deposits of CHF 80.7M as of March 31, 2020
  • Net cash used in operating activities of CHF 12.8M
  • Operating loss of CHF 12.2M and net loss of CHF 13.3M in Q1 20
  • Company funded into H2 2021, not including potential milestones from ongoing partnerships

 

Zurich-Schlieren, Switzerland, May 7, 2020. Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company that is developing a new class of custom-built protein therapeutics known as DARPin® therapeutics, announced today its interim management statement for the period ending March 31, 2020.

“We have responded to the current global pandemic in three ways: ensuring the safety of our employees and other stakeholders; preserving continuity of operations with appropriate safeguards; and initiating an accelerated anti-COVID-19 program to leverage the compelling advantages of the DARPin® platform against the novel coronavirus. As we prepare for the FDA’s decision regarding abicipar, which would be the first approved DARPin® therapeutic, we have continued to progress our broad pipeline of next-generation multi-DARPin® candidates,” said Patrick Amstutz, Ph.D., Chief Executive Officer of Molecular Partners. “Our focus as ever is excellence in scientific innovation executed by a team united by a common purpose to deliver an entirely new class of medicine.”

Clinical Updates:

MP0250 in multiple myeloma

MP0250 is a multi-DARPin® candidate that targets hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), two prominent tumor escape pathways, and has the potential to reverse adaptive resistance to standard-of-care cancer therapies.

The first phase 2 trial for MP0250 in combination with proteasome inhibitors (PIs) is evaluating MP0250 in combination with bortezomib (Velcade®) and dexamethasone in patients with multiple myeloma who have failed standard therapies. As of April 30th, 2020, thirty patients have been enrolled at the 8mg/kg cohort in its ongoing study MP0250-201. 5/30 patients still receiving treatment will be monitored and treated, per protocol. The company will not enroll any additional patients into this study. As discussed at the December 2019 R&D Day, the company is focusing on identifying collaborators best placed to accelerate this program.

 

Phase 1 trial of AMG 506 (MP0310) continues dose escalation

For AMG 506 (MP0310), the phase 1 MP0310-CP101 trial is ongoing and dose escalation is underway. The trial will enroll up to 54 patients at three sites in France to evaluate the safety, tolerability and pharmacokinetics of AMG 506 (MP0310) in patients with locally advanced or metastatic solid tumors. 

 

MP0317 (FAP x CD40) IND-enabling work continues to progress

In Q4 2019, Molecular Partners nominated tumor-localized immune agonist MP0317 as the second DARPin® protein in the company’s immuno-oncology pipeline. MP0317 comprises localizer (FAP) and stimulator (CD40) DARPin® domains. It is designed to activate immune cells specifically in the tumor and not in the rest of the body, potentially delivering greater efficacy with fewer side effects. Preclinical data demonstrated that the company’s multi-specific FAP x CD40 DARPin® molecule induced FAP-dependent activation of B cells, dendritic cells and macrophages. As previously indicated, the company anticipates filing an IND for MP0317 around the end of 2020.

 

Dosing ongoing in trial for MP0274 in HER2-positive solid tumors

Recruitment for the dose escalation phase of the phase 1 trial of MP0274 continues. MP0274 is a multi-DARPin® product candidate being developed for the treatment of HER2-positive solid tumors. In preclinical trials MP0274 inhibits downstream signaling pathways, and directly kills HER2-addicted tumor cells through the induction of apoptosis. This represents a new and differentiated mode of action as compared to current standard-of-care antibodies.

 

Abicipar: Additional filing in Japan, and data presented demonstrating improved tolerability of Abicipar in the MAPLE study

In February 2020, at the Angiogenesis, Exudation, and Degeneration symposium, a presentation titled “Update on the Safety and Efficacy of Abicipar Pegol” was provided by Baruch D. Kuppermann, M.D., Ph.D. This presentation reviewed data from both, the 2-year follow-up data of the CEDAR and SEQUOIA phase 3 studies as well as the MAPLE study, which was a 28 week open-label study that evaluated Abicipar produced via a modified manufacturing process and has demonstrated a lower inflammation rate than the rate observed in Phase 3 studies.   The data presented showed that in year 2 of the CEDAR and SEQUOIA study and in the MAPLE study there were no incidences of retinal vasculitis.

In March 2020, an application to approve abicipar for the treatment of nAMD was filed to the Japanese Pharmaceuticals and Medical Devices Agency.

Balance sheet: Strong cash and equity positions as of March 2020

Molecular Partners’ financial performance for the first three months of 2020 reflects an operating cash outflow of CHF 12.8 million. Cash and short-term deposits decreased by CHF 14.4 million in Q1 2020 to CHF 80.7 million as of March 31, 2020 (year-end 2019: CHF 95.1 million).

As of March 31, 2020, the company employed 139.6 FTEs, a 14% increase year-over-year, with approximately 85% of employees serving in R&D functions.

Business outlook and priorities

In 2020, Molecular Partners anticipates regulatory decisions by the FDA and European Medicines Agency (EMA) regarding the market launch of abicipar for patients with nAMD. The FDA is expected to take action on the Biologics License Application (BLA) by mid-2020, and a decision from the European Commission is expected in the second half of 2020. Molecular Partners continues to work closely with its partner Allergan in the preparation and education of the market for the expected launch.

In immuno-oncology, recruitment of patients will continue in the phase 1 trial of MP0310 (AMG 506). Molecular Partners and Amgen expect to collect initial data from this trial in H2 2020.

In oncology, the company intends to conclude its phase 2 trial of MP0250 in patients with multiple myeloma in combination with Velcade® and will pursue partnership opportunities for the MP0250 program. The company further plans in 2020 to establish dosing and clinical strategy for MP0274, as that therapeutic candidate concludes its phase 1 dose escalation.

Additionally, Molecular Partners will continue to advance its immuno-oncology research pipeline, specifically the MP0317, the CD3 DARPin® T cell-engager platform and peptide-MHC programs.

Financial outlook 2020

For the FY 2020, at constant exchange rates, the company continues to expect total expenses of CHF 60-70 million, of which around CHF 6 million will be non-cash effective costs for share-based payments, International Financial Reporting Standards (IFRS) pension accounting and depreciations.

This guidance is subject to the progress of the pipeline, mainly driven by manufacturing costs, the speed of enrollment of patients in clinical trials and data from research and development projects; in addition to potential external impacts such as the ongoing COVID-19 global pandemic. No guidance can be provided with regard to net cash flow projections. Timelines and potential milestone payments for existing and potentially new partnerships are not disclosed.

Financial Calendar

August 26, 2020 Publication of Half-year Results 2020 (unaudited)
October 29, 2020 Interim Management Statement Q3 2020

http://investors.molecularpartners.com/financial-calendar-and-events/

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 a new class of custom-built proteins known as DARPin® therapeutics, designed to address challenges current modalities cannot. The company has compounds in various stages of clinical and preclinical development with a focus on oncology. Molecular Partners has formed partnerships with leading pharmaceutical companies to advance DARPin® therapeutics across multiple therapeutic areas.

For more information regarding Molecular Partners AG, go to: www.molecularpartners.com.

For further details, please contact:

Seth Lewis, SVP IR, Comms, & Strategy
seth.lewis@molecularpartners.com
Tel: +1 781 420 2361

Tom Donovan, U.S. Media
tom@tenbridgecommunications.com
Tel: +1 857 559 3397

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

Disclaimer

This communication does not constitute an offer or invitation to subscribe for or purchase any securities of Molecular Partners AG. This publication may contain certain forward-looking statements and assessments or intentions concerning the company and its business. Such 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 reliance on these statements, particularly not in connection with any contract or investment decision. The company disclaims any obligation to update these forward-looking statements, assessments or intentions.