Molecular Partners Presents Positive Preclinical Data for First Switch-DARPin Candidate MP0621 at EHA 2024
Molecular Partners has revealed promising preclinical data for MP0621, their first Switch-DARPin candidate, at the European Hematology Association 2024. MP0621 targets cKit-positive cells and conditionally blocks CD47 to facilitate hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML) patients. The candidate showed selective cell killing and minimal systemic side effects in vivo, validating the Switch-DARPin concept. Preclinical studies demonstrated effective cKit+ cell depletion and a pharmacokinetic profile suitable for HSCT therapy. Phase 1 clinical trials for MP0621 are scheduled for 2025.
- MP0621 demonstrated selective killing of cKit-positive cells, reducing risk to healthy cells.
- The preclinical data support MP0621's potential for safer and more effective HSCT in AML patients.
- MP0621 showed minimal systemic side effects in preclinical studies.
- The pharmacokinetic profile of MP0621 is suitable for HSCT therapy.
- Phase 1 clinical trials for MP0621 are planned for 2025, indicating a clear development timeline.
- MP0621 is currently only in preclinical stages, with human efficacy and safety not yet confirmed.
- Potential risks include failure in upcoming clinical trials or unforeseen side effects.
- The long development timeline may lead to delays and increased costs before potential market approval.
Insights
The preclinical data for MP0621 highlights the innovative potential of Molecular Partners' Switch-DARPin platform. This technology presents a novel approach to conditionally activate immune cells, reducing systemic side effects often associated with therapies targeting CD47, a important immune checkpoint protein. The specificity and efficacy demonstrated in targeting cKit-positive cells, which are essential for stem cell maintenance, are promising, particularly for patients with acute myeloid leukemia (AML) undergoing hematopoietic stem cell transplantation (HSCT).
In simple terms, the ability of MP0621 to selectively inhibit CD47 only on cKit-positive cells could revolutionize HSCT by enhancing the destruction of diseased cells while minimizing damage to healthy cells. This approach could significantly reduce the need for high-intensity conditioning regimens, thus lowering associated risks and improving patient outcomes.
Moreover, the preclinical results indicate that MP0621 performs comparably to combinations of existing monoclonal antibodies but with potentially fewer side effects. This positions Molecular Partners favorably in the competitive landscape of AML treatments, offering a unique mechanism of action that might address unmet clinical needs.
The announcement of positive preclinical data for MP0621 is a significant milestone for Molecular Partners. Investors should note that while this news is promising, it remains within the preclinical phase. The projected initiation of Phase 1 clinical trials in 2025 indicates a long development timeline, which means any potential market impact is still several years away.
Financially, the validation of the Switch-DARPin platform could attract further investment and partnership opportunities, especially given its potential applications in high-need areas such as AML. However, the long road to commercialization and regulatory approval must be considered. The company's ability to manage costs and maintain a strong balance sheet during this period will be crucial.
Additionally, the positive data might boost Molecular Partners' stock in the short term, reflecting increased investor confidence. Yet, a cautious approach is advisable, as further clinical trials will determine the ultimate viability of MP0621.
- Proof-of-concept of Switch-DARPin platform established in vivo, enabling the use of logic-gated and reversible immune activators
- Preclinical safety, efficacy, and pharmacokinetics support MP0621’s potential to selectively kill cKit-positive cells and conditionally block CD47 with limited systemic side effects
- MP0621 presently in IND-enabling studies with Phase 1 in AML anticipated in 2025
ZURICH-SCHLIEREN, Switzerland and CONCORD, Mass., June 14, 2024 (GLOBE NEWSWIRE) -- Ad hoc announcement pursuant to Art. 53 LR Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, today announced preclinical proof-of-concept data from MP0621, a multispecific cKit x CD16a x CD47 Switch-DARPin program. The data validates the Switch-DARPin concept in vivo and MP0621’s potential as a next-generation therapeutic supporting hematopoietic stem cell transplantation (HSCT), initially for the treatment of acute myeloid leukemia (AML) patients. The data will be presented today in a poster session at the European Hematology Association (EHA) 2024 Hybrid Congress taking place June 13-16 in Madrid, Spain.
“We designed our Switch-DARPin platform to unlock undruggable targets and enable safe use of powerful immune activators via logic-gated and reversible immune activation,” said Anne Goubier, Ph.D., SVP Research & Early Development. “MP0621 is our first candidate in this series, with the aim to clear HSCs effectively and safely, by targeting cKit, engaging innate immune cells via CD16a, and blocking CD47 only on cKit+ cells. We’re thrilled by these results, which validate our Switch-DARPin platform in vitro and in vivo and pave the way for a new generation of conditionally activated T cell engagers, with the potential to revolutionize therapy in areas of unmet need, such as solid tumors”.
HSCT offers a potential cure for patients with AML and other malignant and non-malignant diseases. However, the toxicity of pre-HSCT conditioning often requires that it is carried out with reduced intensity, increasing the likelihood that diseased cells remain in the bone marrow and lead to relapse. Safer and more efficacious treatments are needed to improve HSCT outcomes for more patients with AML and other diseases requiring HSC transplant. MP0621 is intended to maximize the therapeutic potential of HSCT for AML patients, including those with poor cytogenetic risk profile, to extend the access to potentially curative HSCT for more patients, and to increase long term disease control post HSCT.
MP0621 is designed to induce eradication of HSCs while avoiding the toxicity associated with current high-intensity conditioning regimens. MP0621 engages natural killer cells and macrophages via CD16a to selectively kill targeted cKit-positive cells. cKit is critical for stem cell maintenance and renewal and thus an attractive target to select for HSCs as well as leukemic stem cells in AML. CD47 is widely expressed as “don’t-eat-me” signal and prevents killing of cells, including HSCs/LSCs. Blocking CD47 can enhance damage to bound stem cells; however systemic anti-CD47 blockers cause significant toxicity, highlighting the need for conditional and targeted blockade of CD47.
The Switch-DARPin platform provides a logic-gated “on/off” function (the “Switch”) to multispecific DARPin candidates leading to target activation only in the presence of defined antigens. In MP0621, the Switch-DARPin binds to either cellular cKit or to the anti-CD47 DARPin binder. Upon MP0621 binding to cKit on cells, the Switch-DARPin will unmask the anti-CD47 DARPin, which in turn will bind CD47 and block the “don’t-eat-me” signal, leveraging the power of CD47 inhibition without its associated toxicity to healthy cells. The Company is presently conducting preclinical efficacy and safety studies for MP0621 with data expected in H2 2024.
In the poster presented, preclinical studies demonstrate that:
- MP0621 selectively blocks CD47 on cells expressing cKit
- Conditional blockade of CD47 enhances efficacy of cKit targeting, with phagocytosis comparable to a combo of anti-cKit and anti-CD47 monoclonal antibodies
- MP0621 depleted cKit+ cells in bone marrow of humanized mice without affecting circulating immune cells
- PK profile of MP0621 is suitable for HSCT therapy in humans
Poster details can be found below. The full poster will be made available on Molecular Partners' website after the presentation.
Title: C-KIT X CD16A X CD47 Switch-DARPin with Conditional Blockade of CD47: A Next-generation Targeted Conditioning for Hematopoietic Stem Cell Transplantation
Session Title: Stem Cell Transplantation – Experimental
Abstract Number for Publication: P1294
Poster Session Timing: June 14, 2024; 6-7 pm CET
About Molecular Partners AG
Molecular Partners AG is a clinical-stage biotech company pioneering the design and development of DARPin therapeutics for medical challenges other drug modalities cannot readily address. The Company has programs in various stages of pre-clinical and clinical development, with oncology as its main focus. Molecular Partners leverages the advantages of DARPins to provide unique solutions to patients through its proprietary programs as well as through partnerships with leading pharmaceutical companies. Molecular Partners was founded in 2004 and has offices in both Zurich, Switzerland and Concord, MA, USA. For more information, visit www.molecularpartners.com and find us on LinkedIn and Twitter/X @MolecularPrtnrs.
For further details, please contact:
Seth Lewis, SVP Investor Relations & Strategy
Concord, Massachusetts, U.S.
seth.lewis@molecularpartners.com
Tel: +1 781 420 2361
Laura Jeanbart, PhD, Head of Portfolio Management & Communications
Zurich-Schlieren, Switzerland
laura.jeanbart@molecularpartners.com
Tel: +41 44 575 19 35
Cautionary Note Regarding Forward-Looking Statements
Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation: implied and express statements regarding the clinical development of Molecular Partners’ current or future product candidates; expectations regarding timing for reporting data from ongoing clinical trials or the initiation of future clinical trials; the potential therapeutic and clinical benefits of Molecular Partners’ product candidates and its RDT and Switch-DARPin platforms; the selection and development of future programs; Molecular Partners’ collaboration with Orano Med including the benefits and results that may be achieved through the collaboration; and Molecular Partners’ expected business and financial outlook, including anticipated expenses and cash utilization for 2024 and its expectation of its current cash runway. These statements may be identified by words such as “anticipate”, “believe”, “expect”, “guidance”, “intend”, “may”, “plan”, “potential”, “will”, “would” and similar expressions, and are based on Molecular Partners’ current beliefs and expectations. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Some of the key factors that could cause actual results to differ from Molecular Partners’ expectations include its plans to develop and potentially commercialize its product candidates; Molecular Partners’ reliance on third party partners and collaborators over which it may not always have full control; Molecular Partners’ ongoing and planned clinical trials and preclinical studies for its product candidates, including the timing of such trials and studies; the risk that the results of preclinical studies and clinical trials may not be predictive of future results in connection with future clinical trials; the timing of and Molecular Partners’ ability to obtain and maintain regulatory approvals for its product candidates; the extent of clinical trials potentially required for Molecular Partners’ product candidates; the clinical utility and ability to achieve market acceptance of Molecular Partners’ product candidates; the potential that Molecular Partners’ product candidates may exhibit serious adverse, undesirable or unacceptable side effects; the impact of any health pandemic, macroeconomic factors and other global events on Molecular Partners’ preclinical studies, clinical trials or operations, or the operations of third parties on which it relies; Molecular Partners’ plans and development of any new indications for its product candidates; Molecular Partners’ commercialization, marketing and manufacturing capabilities and strategy; Molecular Partners’ intellectual property position; Molecular Partners’ ability to identify and in-license additional product candidates; unanticipated factors in addition to the foregoing that may impact Molecular Partners’ financial and business projections and guidance; and other risks and uncertainties that are described in the Risk Factors section of Molecular Partners’ Annual Report on Form 20-F for the fiscal year ended December 31, 2023, filed with Securities and Exchange Commission (SEC) on March 14, 2024 and other filings Molecular Partners makes with the SEC. These documents are available on the Investors page of Molecular Partners’ website at www.molecularpartners.com. Any forward-looking statements speak only as of the date of this press release and are based on information available to Molecular Partners as of the date of this release, and Molecular Partners assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise.
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