Corporate Presentation
June 14, 2024
1
Disclaimer
This presentation contains forward looking statements. Any statements contained in this presentation 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, the selection and development of future programs, 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 "guidance", "believe", "expect", "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 may cause Molecular Partners' actual results and outcomes to materially differ from its 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 presentation 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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The DARPin Modality and Molecular Partners' Strategy
DARPin
Target
What we invented
- New class of therapeutics: Designed Ankyrin Repeat Proteins (DARPins)
- DARPins to close the gap between small molecules and antibodies
- 7 clinical-stage compounds, >2500 patients treated
How we apply it
- Unique DARPin solutions for a defined medical problems not addressable by antibody designs
- Demonstrate true patient value with early clinical readouts
- Combine our capabilities with world-classpartners to deliver innovative therapeutics
3
Corporate Highlights
MP0533 | • | Novel tetra-specificT cell engager for R/R AML and high-risk MDS/AML patients |
• | ASH 2023: encouraging initial clinical data with acceptable safety and initial antitumor activity | |
• | Phase 1/2a study with dose-escalation well on track; dosing patients in DR 7 ongoing |
Radio-DARPin
Therapy (RDT)
& MP0712
- Successful RDT platform optimization to reduce kidney accumulation and increase tumor uptake
- Announced MP0712 as lead DLL3-targeted212Pb-labelled RDT to be co-developedwith Orano Med
- Preclinical data on MP0712 presented at SNMMI 2024: positive tumor to kidney ratio, efficacy & safety
Switch-DARPin & MP0621
- Demonstrated conditional, target-specific immune activation for Switch-DARPinplatform
- First program: MP0621, a cKit x CD16a x CD47 Switch-DARPin, as next-gen therapeutic supporting HSCT for AML patients & beyond; MP0621 selected as lead candidate to move into development
- Initial preclinical data presented at EHA 2024 indicate encouraging efficacy and safety profile
MP0317 | • | Bi-specific CD40 agonist targeting FAP for tumor-localized immune activation: Favorable safety |
profile and confirmed tumor-localized CD40 activation leading to remodeling of TME in patients | ||
Operations | • | Strong financial position with CHF ~174 M in cash as of March 31, 2024 |
• | Capitalized well into 2026 |
AML, acute myeloid leukemia; ASH, American Society of Hematology; DLL3, Delta-like ligand 3; DR, dose-regimen; EANM,
European Association of Nuclear Medicine; FAP, fibroblast activation protein; MDS, myelodysplastic syndrome; RDT, Radio- 4 DARPin Therapy; R/R, relapsed/refractory; SITC, Society for Immunotherapy of Cancer; TME, tumor microenvironment.
Pipeline | ||||||
MODALITY | CANDIDATE | RESEARCH | PRE-CLINICAL | PHASE 1 | PHASE 2 | RIGHTS |
Tetra-specific | MP0533 | R/R AML and AML / MDS | ||||
T cell Engager | CD33 x CD123 x CD70 x CD3 | |||||
MP0712 | SCLC & NETs | |||||
Radio-DARPin | DLL3 | Co-development* | ||||
Therapy | Undisclosed | Solid | ||||
Programs | Tumors | In-house programs | ||||
Undisclosed | Solid | |||||
Programs | Tumors | 2 partnered programs | ||||
MP0621 | AML / HSCT | |||||
Switch-DARPin | cKIT x CD16a x CD47 | |||||
Undisclosed | Immune cell | |||||
Program | engager | |||||
Localized | MP0317 | Advanced Solid Tumors | ||||
Agonist | FAP x CD40 | |||||
*The co-development agreement with Orano Med includes up to 3 potential oncology targets including DLL3. | 5 |
AML, acute myeloid leukemia; DLL3, Delta-like ligand 3; HSCT, hematopoietic stem cell transplant; |
MDS, myelodysplastic syndrome; NET, neuroendocrine tumor; R/R, relapsed/refractory; SCLC, small cell lung cancer.
MP0533
Tetra-specificT-cell Engager for AML
6
Patients with AML Have a High Unmet Medical Need
69 OLD | 31.7% |
YEARS | |
Median age of AML | Overall 5-year |
patients at diagnosis1 | survival rate1 |
Despite 50 years of progress, elderly and frail patients are often not eligible for high-intensity conditioning and HSCT, and thus have limited treatment options and poor survival outcomes2
- Lack of broad and clean AML surface targets
- Risk of clonal escape even after high-intensity conditioning/HSCT
SURVIVAL RATE (%)
80
70
60
50
40
30
20
10
0
5-year survival rate
by age and treatment era2
Younger patients (< 60 years)
Older patients (>= 60 years)
1970s | 1980s | 1990s | 2000s | 2010s |
TREATMENT ERA (DECADE)
1.https://seer.cancer.gov/statfacts/html/amyl.html(based on data: 2016-2020;accessed 3 Jan 2024) | 7 |
2. Kantarjian HM, et al. Clin Lymphoma Myeloma Leuk 2021; 21:580-597. | |
AML, acute myeloid leukemia; HSCT, hematopoietic stem cell transplantation. |
MP0533: Avidity-Driven Selectivity for Cancer Cells in AML
Problem: AML tumor-associated antigens are expressed on healthy cells
AML cells
Healthy cells
CD33 | • AML remains a deadly disease and persistence of leukemic stem cells |
CD123 | (LSCs) drives relapse |
CD70 | • AML cell population is heterogeneous: individual AML blasts and LSCs lack |
a clean target. AML cells can be differentiated from healthy cells (e.g. HSCs) | |
by their co-expression of specific targets (e.g. CD33, CD123, CD70) |
HSA | HSA | CD33 | CD123 | CD70 | CD3 |
Solution: MP0533 - Avidity-driven selectivity and killing by T cells
T cell | T cell |
Half-life extender | Target localizers | Immune |
activator |
• MP0533 is designed to induce T cell-mediated killing preferentially when
HSA | two or three target antigens (CD33, CD123, CD70) are co-expressed | ||
killing | • MP0533 is hypothesized to preserve healthy cells hence opening a | ||
therapeutic window | |||
• MP0533 has the potential to kill all AML cells (blasts and LSCs) despite | |||
Healthy cell | AML cell | heterogeneity, ensuring long term disease control |
AML, acute myeloid leukemia; HSC, hematopoietic stem cell; HSA, human serum albumin. | 8 |
MP0533 Phase 1 Dose-escalation Trial in R/R AML patients
PHASE 1 | PHASE 2A |
DR ESCALATION OF MP0533 MONOTHERAPY | POC OF MP0533 MONOTHERAPY |
STUDY DESIGN
- FIH, multicenter, single-arm,open-label, Phase 1/2a study of MP0533 monotherapy (NCT05673057)
- Objectives: Safety/tolerability, PK/PD, and preliminary activity
- Eligible patients: Adults with R/R AML or MDS/AML
- Centers: 9 sites initiated across Europe
n=3
DR 3
n=1
DR 2
n=1
DR 1
n=8
DR 5
n=6
DR 4
DR 7
DOSING
n=3-9 | Expansion |
with RP2D-R | |
DR 7 |
n=9
DR 6
n=30
Step up dosing in cycle 1 (= DLT period) of each DR
D1 | D5 | D8 | D15 | D22 |
week 2 | week 3 | week 4 |
Study currently dosing patients in DR 7, plans to update in H2 2024
AML, acute myeloid leukemia; D, treatment cycle day; DLT, dose-limiting toxicity; DR, dose regimen; FIH, first-in-human; | 9 |
MDS, myelodysplastic syndrome; n, number of patients; PD, pharmacodynamic; PK, pharmacokinetics; POC, proof of |
concept; RP2D-R, recommended phase 2 DR; R/R, relapsed/refractory.
MP0533 - Patient Characteristics and Safety Profile
PATIENT CHARACTERISTICS | DR COHORTS 1-6 (n=28) |
Sex, n (%) |
MP0533-RELATED TEAEs‡
Female / male | 14 (50) / 14 (50) | |||
Age | ||||
Mean / Median (range) | 68 | / 74 (22-82) | ||
ECOG PS, n (%) | ||||
0 / 1 / 2 | 11 | (39) | / 14 (50) / 3 (11) | |
Hematologic malignancy, n (%) | ||||
AML / MDS/AML | 19 | (68) | / 9 | (32) |
ELN risk category, n (%) | ||||
Intermediate / adverse | 4 (14) / 24 | (86)* | ||
No. of prior systemic treatment | ||||
lines, n (%) | 12 | (43) | / 9 | (32) / 7 (25) |
1 / 2 / ≥3 |
*TP53 mutated: 7 (25%)
Acceptable safety profile for MP0533 reported for DR 1-6‡:
- IRR and CRS are the most frequent MP0533-related TEAEs (mostly Grade 1-2, occasional Grade 3)
- No DLTs up to DR 6
Ventricular extrasystoles Renal failure Pneumonia Platelet count decreased Neutropenic colitis Nausea Lymphopenia
Lymphocyte count decreased Intervertebral discitis Infusion related reaction Hepatic cytolysis Immune reaction Headache Erythema multiforme Erysipelas
Dissiminated intravascular coagulation Cytokine release syndrome Cellulitis Blood fibrinogen decreased Bacteraemia
Angina unstable Alanine aminotransferase increased
1 | Grade 1 | = Mild | |
1 | Grade 2 = Moderate | ||
1 | Grade 3 | = Severe | |
Grade 4 | = Life threatening | ||
3 | |||
2 | |||
35 | 19 | ||
1 | |||
2 | |||
1 |
1813
1
1
Data cut-off: 12 March 2024 | ‡ TEAEs of n=1 of grade 1 were removed from the graph for display purposes. | 10 |
AE, adverse event; CRS, cytokine release syndrome; ELN, European | ||
Preliminary data as study is ongoing, subject to final data validation. | ||
LeukemiaNet; IRR, infusion-related reaction; TEAE, treatment-emerging AE. | ||
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Molecular Partners AG published this content on 14 June 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 14 June 2024 07:06:27 UTC.