Merus. Corporate Presentation. November 15, 2018

Transcription

1 Merus Corporate Presentation November 15, 2018

2 Disclaimer This presentation (including any oral commentary that accompanies this presentation) contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of All statements contained in this presentation that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the impact our Biclonics platform can have on cancer, our product candidates' potential to treat certain types of tumors, the timing of regulatory filings and the timing and anticipated results from our clinical trials. These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have incurred significant losses, are not currently profitable and may never become profitable; our need for additional funding, which may not be available and which may require us to restrict out operations or require us to relinquish rights to our technologies or bispecific antibody candidates; potential delays in regulatory approval, which would impact our ability to commercialize our product candidates and affect our ability to generate revenue; the unproven approach to therapeutic intervention of our Biclonics technology; our limited operating history; economic, political, regulatory and other risks involved with international operations; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; the unpredictable nature of our early stage development efforts for marketable drugs; potential adverse public reaction to the use of cancer immunotherapies; potential delays in enrollment of patients, which could affect the receipt of necessary regulatory approvals; failure to obtain marketing approval internationally; failure to compete successfully against other drug companies; potential competition from other drug companies if we fail to obtain orphan drug designation or maintain orphan drug exclusivity for our products; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; protection of our proprietary technology; our patents being found invalid or unenforceable; potential lawsuits for infringement of third-party intellectual property; our ability to attract and retain key personnel; managing our growth could result in difficulties; and we may lose our foreign private issuer status and incur significant expenses as a result. These and other important factors discussed under the caption Risk Factors in our Annual Report on Form 20-F filed with the Securities and Exchange Commission, or SEC, on April 30, 2018, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this presentation. Any such forward-looking statements represent management's estimates as of the date of this presentation. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change 2

3 Company Highlights Oncology focus Proprietary pipeline Unique technology platform Productive discovery engine Well Capitalized Differentiated pipeline of bispecific antibodies that target cancer (stem) cells, enhance tumor immunity or modulate the tumor micro-environment MCLA Phase 2 in metastatic breast cancer (mbc), Phase 1 (other solid tumors) MCLA Phase 1 in acute myeloid leukemia (AML) MCLA Phase 1 in solid tumor space, initial focus on metastatic colorectal cancer MCLA IND enabling studies ongoing for multiple solid tumors Biclonics Platform - full length IgG human bispecific antibodies provides for functional screening, reliable manufacturing and predictable behavior in patients In-format functional screening interrogating target combinations for novel biology and modes of action fuels a rich pipeline of differentiated Biclonics Powered by efficient manufacturing process 224.1m cash, cash equivalents and investments as of June 30, 2018 Expected cash runway through year end 2020 Expected funding through key clinical milestones 3

4 Merus Biclonics - Closing in on cancer with bispecific antibodies Biclonics : The natural antibody format enhanced for: dual target binding to more potently kill tumor cells novel modes of action Natural antibody Biclonics T Cell Tumor Cell Novel modes of action T cell engager Exhausted T Cell Revival of tumorspecific T cells single target binding dual target binding Targeting the tumor micro-environment 4

5 Merus Biclonics Technology Platform Pragmatic design and candidate selection, predictable in vivo behavior Diversity, high quality Tailor-made activity Attractive drug properties Predictability Human antibodies MeMo transgenic mouse Fc region-based functional flexibility Fc silencing Enhanced ADCC Antibody properties in patients Long half life Low immunogenicity Robust manufacturing High purity and yield immune cell recruitment Silencing added safety 5

6 Merus Functional Screening for Differentiated Product Leads Cell-based functional screening of large collections of Biclonics yields product leads with desirable and novel modes of action (MOI) DC Large collection ( 1000) of Biclonics Functional activity Desirable MOI [ CD8+ T cell Primary functional screen Additional screens Tumor cell Functional screening in cell-based assays In vivo validation lead Lead selection Desirable/novel MOI # Biclonics 6

7 Robust Pipeline Targeting Solid and Hematological Tumors Program Targets Indication/drug combination Pre- IND/CTA Phase 1 Phase 2 Merus rights MCLA-128 HER2, HER3 Breast (HER2+) + Herceptin + chemo worldwide Breast (ER+) + hormone therapy worldwide Solid tumors (monotherapy)* worldwide MCLA-117 CD3, CLEC12A AML worldwide MCLA-158 EGFR, Lgr5 Solid tumors worldwide MCLA-145 PD-L1, undiscl. Solid tumors Collaboration with Incyte Corporation US Undisclosed Autoimmune disease Collaboration with Ono Pharmaceutical N/A *Phase 1/2 Discovery Engine utilizing Biclonics Platform and Functional Screening to identify future pipeline candidates 7

8 MCLA-128 Biclonics that potently inhibits the HER3 pathway, a driver of tumor growth and survival

9 MCLA-128 Targeting the HER3 Pathway Heregulin-driven signalling via the HER2:HER3 heterodimer promotes: primary tumor cell proliferation treatment escape/relapse (HER2 and EGFR blockade, hormone therapy, chemotherapy) HER2:HER3 heterodimer MCLA-128 heregulin heregulin heregulin paracrine autocrine Tumor growth Treatment escape 9

10 MCLA-128 Unique Mechanism of Action Unbiased Combinatorial Screening Identifies a Bispecific IgG1 that Potently Inhibits HER3 Signaling via HER2-Guided Ligand Blockade Cecile A.W. Geuijen, et. al., Cancer Cell 2018 Dock on HER2, abundantly expressed on tumor cells Block HER3 signaling, even under high heregulin stress Enhanced ADCC - efficient recruitment of immune killer cells More effective than Herceptin (H) + Perjeta (P) Preclinical Studies show more effective than Herceptin (H) + Perjeta (P) Percent survival % survival of mice vehicle MCLA-128 H + P Days 10

11 MCLA-128 Phase 2 Clinical Trial in Metastatic Breast Cancer Breast Cancer Phase 1 Monotherapy Single agent activity established Phase 2 Combination therapy MBC Cohort 1 HER2+ MCLA Herceptin + chemo MBC Cohort 2 ER+/ HER2 low MCLA hormone therapy Size: up to 120 Patients in U.S and Europe Dose: 750 mg every 3 weeks Primary endpoint: clinical benefit at 24 wks 11

12 MCLA-128 Phase 1 Clinical Trial in Solid Tumors Gastric Cancer Endometrial/Ovarian/NSCL cancer Single agent activity established Trials ongoing Phase 1 Monotherapy Clinical Proof of Concept Established Phase 2 Evaluation of combination & development options under consideration 12

13 MCLA-117 CD3 x CLEC12A T cell engager Biclonics binding a first-in-class target expressed on acute myeloid leukemia (stem) cells

14 Biclonics T Cell Engagers T cell engagers harness the killing power of T lymphocytes One arm of the Biclonics binds to CD3 expressed on T lymphocytes One arm of the Biclonics binds to a tumor-associated antigen (TAA) Activity Toxicity Advantages of Biclonics T cell engagers T Cell CD3 TAA Tumor Cell Safety Low affinity CD3 arm for controlled T cell activation Silenced Fc region to prevent off target T cell activation Pharmacokinetic/dynamic properties Human full length IgG long half life attractive dosing schedule low immunogenicity 14

15 MCLA-117 Restricted Tissue Expression of CLEC12A Erythrocyte CD123/CD33 Common myeloid progenitor Megakaryocyte/erythroid stem cell Platelet Basophil Hematopoietic stem cell CLEC12A Granulocye/macrophage stem cell Neutrophil Eosinophil Common lymphoid progenitor Monocyte CLEC 12A expression Normal tissues Not expressed outside of the hematopoietic system Only on certain myeloid cells. More restricted expression than CD33 and CD123 Tumor tissues Expressed by tumor cells of ~90-95% of patients with AML (> 85% of patients with MDS) Expressed by AML tumor stem cells Potential advantages of Merus approach to CLEC12A Spares erythrocytes and platelets More efficient recovery from neutropenia Less toxicity outside of the hematopoietic system 15

16 MCLA A First in Class Target for AML Tumor (Stem) Cells % CLEC12A Stem cells CLEC12A expression on AML but not on normal hematopoietic stem cells % AML BM Normal BM Potential advantages Elimination of leukemic stem cells More efficient recovery from neutropenia Sparing red blood cell and platelet formation Recovery potential of BM after depletion of CD34+/CLEC12A+ or CD34+/CD33- cells # colonies CD33- CLEC12A- M-L M E M-L M E Recovery of multi-lineage (M-L), myeloid (M) and erythroid (E) cells in CD34+ normal BM cells Van Rhenen et al., Blood 110, 2659 (2007) Zheng et al., Clin Can Res June

17 MCLA-117 Phase 1 Trial Phase 1 Trial Minimum Anticipated Biological Effect Level (MABEL) approach determined starting dose, related to inherent potent activity of T cell engagers Eligible AML Patient Population All AML subtypes except M3 Relapsed /refractory patients > 18 years old Treatment naïve patients > 65 years of age Trial Status Trial is ongoing and progressing as expected Formal update once the Maximum Tolerated Dose (MTD) is reached All T cells: no requirement for tumor-specific T cells Potent Activity T Cell CD3 TAA Doselimiting Toxicity Tumor Cell 17

18 MCLA-158 Biclonics specific for EGFR x Lgr5 that potently blocks EGFR signaling in Wnt-activated solid tumors

19 MCLA-158 Differentiated Mode of Action for Unmet Medical Need A cancer initiating-cell targeting Biclonics that, in preclinical studies, has shown: higher potency than EGFR targeting mab, Cetuximab to effectively eliminate tumor stem cells in vitro and in vivo (KRAS WT and KRAS Mut ) lack of skin toxicity (rash) in cynomolgous monkey studies Unmet Medical Need Differentiated Mode of Action Designed to eliminate cancer initiating cells that cause relapse and metastasis RAS Mut colorectal cancer represents approximately 50% of disease Potently blocks EGFR signaling in Wnt activated tumors and induces apoptosis Enhanced ADCC for immune effector cell recruitment MCLA-158 has potential to address features that limit currently approved colorectal cancer-targeted therapies and address a broader population of patients more effectively 19

20 Lgr5+ Cells Are the Origin of Gastrointestinal Cancer Intestinal cancer-initiating cells express Lgr5 Lgr5+ cells can be expanded in vitro to form organoids Lgr5+ cell MCLA-158 validated in organoid-based screening Mechanism of action: Induction of apoptosis & ADCC compounds feature measurements EGFR Cancer Stem Cell Lgr5 Cancer Stem Cell NK cell Cancer Stem Cell Apoptosis Enhanced ADCC 20

21 MCLA-158 Key Pre-Clinical Results in Colorectal Cancer (CRC) In preclinical studies, Merus observed greater growth inhibitory activity of 158 against colon tumors than normal tumor tissue Inhibition of organoid growth in PDX models Superior activity compared to Cetuximab % survival P e r c e n t s u r v i v a l P= D a y s e l a p s e d days elapsed No antibody Cetuximab MCLA-158 P = Safely dosed in Cynomolgous monkeys MCLA-158 dose: 0, 2.5, 7.5 or 25 mg/kg Time (days) Terminal evaluations No change in organ weight or ratio No macroscopic or microscopic findings Normal IgG pk Killing of organoids from tumor & healthy tissue Superior selectivity compared to Cetuximab N o r m a l i z e d T u m o r o i d s i z e Organoid size T u m o r C o l o n p t C 5 5 N o r m a l C o l o n p t C 5 5 M C L A C 5 5 T C e t u x i m a b C 5 5 T > 100-fold D o s e ( l o g µ g /m Dose (log µg/ml) M C L A C 5 5 N Tumor colon C e t u x i m a b C 5 5 N Cetuximab MCLA-158 Normal colon Cetuxmab MCLA

22 MCLA-158 Phase 1 Trial MCLA-158 Phase 1 Trial Design Patient Open-label, population multicenter clinical trial First patient dosed in the EU in May 2018 Two parts: dose escalation followed by dose expansion Primary Endpoint: Safety and tolerability of the defined dose in patients with solid tumors Secondary Endpoint: Evaluate preliminary anti-tumor activity of single-agent MCLA

23 Merus - Closing in on Cancer with Bispecific Antibodies Differentiated pipeline with multiple proprietary programs in clinical development Program MCLA-128 MCLA-117 MCLA-158 MCLA Targets HER2, HER3 CD3, CLEC12A EGFR, Lgr5 PD-L1, undiscl. Undisclosed Indication/drug combination Breast (HER2+) + Herceptin + chemo Breast (ER+) + hormone therapy Solid tumors (monotherapy)* AML Solid tumors Solid tumors Autoimmune disease Pre- IND/CTA Phase 1 Phase 2 Merus rights worldwide worldwide worldwide worldwide worldwide US N/A Program Near term communication MCLA-128 Update for MBC cohort expected 2H 2019 MCLA-117 Update upon announcement of MTD MCLA-158 More guidance to come in 2019 MCLA-145 More guidance to come in 2019 Robust technology platform utilizing Biclonics and functional screening to generate novel lead candidates Biclonics with full length IgG format In-format functional screening Robust manufacturing Predictable in vivo behavior Expected cash runway through year end 2020 provides funding through key clinical catalysts 23

24 Merus Closing in on Cancer with Bispecific Antibodies