Cogent Biosciences, Inc. · NASDAQ:COGT
Cogent Biosciences — Unum Therapeutics — Investor Presentation (January 2019)
39 slides from Cogent Biosciences's investor presentation, Jan 7, 2019
Slide 1: Unum Therapeutics Inc. January 2019
Unum Therapeutics Inc. January 2019 Exhibit 99.1
Slide 2: Forward-Looking Statements and Risk Factors
Forward-Looking Statements and Risk Factors This presentation and the accompanying oral commentary contain forward-looking statements that involve risks, uncertainties and assumptions. If the risks or uncertainties ever materialize or the assumptions prove incorrect, our results may differ materiall
Slide 3: Key Company Highlights
Key Company Highlights NOVEL T CELL THERAPY platforms for cancer Promising ANTI-TUMOR ACTIVITY + FAVORABLE TOLERABILITY PROFILE BROAD PIPELINE with three clinical-stage programs, continuing to grow
Slide 4: ACTR and BOXR: Addressing the Challenges for T Cell Therapies
ACTR Addressing the Challenges for T Cell Therapies Overcoming immunosuppression improving engineered T cell functionality in the solid tumor environment Expanding the universe of T cell therapy targets universal antibody-targeted T cells for hematologic and solid tumor applications BOXR
Slide 5: Product Pipeline
Product Pipeline Product Candidate Indication Pre-Clinical Phase I Phase II Hematologic Cancers ACTR707 + rituximab r/r B cell NHL ACTR087 + rituximab r/r B cell NHL ACTR087 + SEA-BCMA r/r Multiple Myeloma Solid Tumor Cancers ACTR707 + trastuzumab HER2+ cancers BOXR1030 GPC3+ cancers ATTCK-20-03 ATT
Slide 6: ACTR
ACTR
Slide 7: ACTR: Antibody-Targeted T-Cells
ACTR: Antibody-Targeted T-Cells ACTR components Costimulatory + TCR domains: provide signals driving T cell response to tumor cell recognition CD16: naturally occurring Fc receptor responsible for antibody-dependent cellular cytotoxicity (ADCC) Tumor-specific antibodies enable ACTR T-cells to target
Slide 8: A Universal Approach
A Universal Approach A single engineered T-cell product used across many different targets and cancer types Opportunity to leverage a broad set of previously manufactured and clinically tested antibodies Control and Tunability Potential to optimize therapeutic index by adjusting antibody dosing Pote
Slide 9: A Universal Approach for Tumor Cell Killing
A Universal Approach for Tumor Cell Killing Preclinical data show that the same ACTR T cell has the potential to kill different types of cancer cells in the presence of the right targeting antibody Kudo et al., “T lymphocytes expressing a CD16 signaling receptor exert antibody-dependent cancer cell
Slide 10: ACTR construct engineered, manufactured and validated once; breadth of targeting
ACTR construct only needs to be engineered, manufactured, and pre-clinically validated once, allowing accelerated development Ability to leverage prior investment in antibody discovery and development, and available safety data Potential for strategic collaborations with antibody innovators Ability
Slide 11: ACTR Control and Tunability
ACTR Control and Tunability Preclinical data indicate ACTR T cell killing may be adjusted by modulating antibody dose. No similar control exists for current T-cell therapies. In vivo (xenograft) In vitro (tumor cell-line killing) rituximab dose (��g/ml) % cytotoxicity
Slide 12: ACTR Clinical Pipeline
ACTR Clinical Pipeline Rapidly expanding pipeline spanning three clinical programs Product Candidate Indication Pre-Clinical Phase I Phase II Hematologic Cancers ACTR707 + rituximab r/r B cell NHL ACTR087 + rituximab r/r B cell NHL ACTR087 + SEA-BCMA r/r Multiple Myeloma Solid Tumor Cancers ACTR707
Slide 13: Clinical Validation: ACTR in Lymphoma
Clinical Validation: ACTR in Lymphoma Potent activity demonstrated in two multi-center trials with r/r NHL patients ATTCK-20-03: ACTR707 (CD28) + rituximab ATTCK-20-2: ACTR087 (41BB) + rituximab Clear dose-dependent ACTR cell expansion observed Persistence of ACTR cells in all patients while on stud
Slide 14: ACTR + Rituximab Trial Design
ACTR + Rituximab Trial Design Cycles 4+ Rituximab q21 days Response Assessments q42 days Cycle 3 Rituximab 1st Response Assessment DLT Assessment Cycle 2 Rituximab Infuse ACTR Cycle 1 Rituximab Lymphodepleting Chemotherapy Leukapheresis Screening/Eligibility ACTR Manufacturing Optional bridging ther
Slide 15: ATTCK-20-03 Patient Characteristics
ATTCK-20-03 Patient Characteristics Characteristic Dose Level 1 (n=6) Dose Level 2 (n=3) Diagnosis: DLBCL, n (%) 5 (83) 3 (100) Diagnosis: Gr3b FL, n (%) 1 (17) 0 Median age, years (range) 61 (57-76) 58 (47-77) Age ≥ 65 years, n (%) 2 (33) 1 (33) Men, n (%) 5 (83) 2 (67) ≥ 3 prior therapies, n (%) 3
Slide 16: Expansion and Persistence
Expansion and Persistence The median peak expansion in Dose Level 2 > 6x Dose Level 1, suggesting dose-dependent ACTR expansion Persistence observed through 233 days (C12D1) post ACTR administration ACTR T cells demonstrate expansion post-infusion and durable persistence Data snapshot: 02 November 2
Slide 17: ATTCK-20-03 Adverse Events
ATTCK-20-03 Adverse Events Adverse Events of Special Interest (AESI) Subjects with AESI, n Dose Level 1 (n=6) Dose Level 2 (n=3) New malignancy 0 0 Cytokine release syndrome 0 0 Use of therapeutic plasma exchange for any non-disease related AE 0 0 Clinically significant neurologic disorder 0 0 Clini
Slide 18: ATTCK-20-03 Anti-Tumor Activity
ATTCK-20-03 Anti-Tumor Activity Dose Level Response Duration of Response (days) Optional Bridging therapy # prior therapies^ ASCT Refractory* to prior therapy Diagnosis Baseline SPD (cm2) 1 Complete 207+ No 2 no no Gr3b FL 24 1 Complete 180+ Yes 5 yes yes DLBCL 23.4 1 Complete 85 Yes 3 no yes DLBCL
Slide 19: Lymphoma Summary & Next Steps
Lymphoma Summary & Next Steps Summary Clinical testing in two independent trials demonstrates anti-tumor activity with a favorable dose-dependent safety profile in relapsed/refractory aggressive NHL patients ACTR707 selected for further development based on best-in-class potential Next Steps ACTR707
Slide 20: ACTR + SEA-BCMA (ATTCK-17-01)
ACTR + SEA-BCMA (ATTCK-17-01) Collaborating with Seattle Genetics to co-develop and co-commercialize novel ACTR + SGI mAb Potential differentiating characteristics Despite high response rates, durability remains a question for many BCMA targeting assets in development Multiple mechanisms of action e
Slide 21: ATTCK-17-01 Status
ATTCK-17-01 Status Completed first three cohorts in dose escalation, starting at very low antibody doses SEA-BCMA: 0.03 mg/kg (n=1) à 0.1 mg/kg (n=1) à 0.3 mg/kg (n=5) ACTR087: target = 30 x 106 ACTR+ T cells SEA-BCMA well-tolerated with expected pharmacological profile ACTR087 expansion observed in
Slide 22: ACTR expansion and persistence; ATTCK-17-01 Safety
ACTR expansion and persistence ATTCK-17-01 Safety and T Cell Expansion AESI n (%) (Cohorts 1-3; n=7) New malignancy 0 Cytokine release syndrome 1 (14)* Use of therapeutic plasma exchange for any non-disease related AE 0 Clinically significant neurologic disorder 1(14)^ Clinically significant rheumat
Slide 23: ACTR + Trastuzumab (ATTCK-34-01)
ACTR + Trastuzumab (ATTCK-34-01) vehicle ACTR alone ACTR + trastuzumab trastuzumab HER2 CAR Potent xenograft activity First ACTR Solid Tumor Program Combination for the treatment of adult patients with relapsed/refractory HER2+ cancers Intending to enroll patients with HER2+ breast cancer, gastric c
Slide 24: ATTCK-34-01: Study Design Schema
ATTCK-34-01: Study Design Schema Example dose escalation schema (n = 12-24 subjects) Design Adaptive Bayesian design Exploring multiple dose levels of ACTR707 and trastuzumab Dose escalation followed by cohort expansion Objectives Assess safety and tolerability of ACTR707 and trastuzumab Assess anti
Slide 25: ACTR Selectivity in Solid Tumors
ACTR Selectivity in Solid Tumors Many solid tumor antigens (e.g., HER2) exhibit low level expression on some normal tissues On-target, off-tumor toxicity can result from inappropriate attack by CAR-T ACTR demonstrates a threshold effect for cytotoxic killing – minimal activity when antigen is below
Slide 26: BOXR
BOXR
Slide 27: Overcoming Solid Tumor Immunosuppression
Overcoming Solid Tumor Immunosuppression BOXR components (1) Chimeric Receptor: universal ACTR or antigen-specific CAR drives cancer cell targeting and attack + (2) Bolt-On: independent transgene that re-programs T cell biology to improve functionality in the tumor microenvironment (TME) BOXR = Bolt
Slide 28: BOXR Discovery Engine
BOXR Discovery Engine Focus on overcoming three primary mechanisms of immunoregulation in solid tumors: nutrient limitations, T-cell exhaustion, and immunosuppressive cell types Biologic Hypothesis Unique insights into immunoregulation within tumors High Throughput Screening Novel, multi-stage scree
Slide 29: BOXR High Throughput Screening
BOXR High Throughput Screening > 100 genes testing literature-based hypotheses Cytotoxicity Cytokines Proliferation Assess basic T cell function Co-express ACTR / CAR + bolt-on transgene Assess function in simulated solid TME Regulatory T cells Suppressive myeloid cells Nutrient shortages Chronic st
Slide 30: BOXR1030: First BOXR Candidate
BOXR1030: First BOXR Candidate Engineered to improve T cell metabolism in solid TME Lung and liver tumors deplete glucose in the tumor Low glucose compromises T cell function, correlates with poor patient outcomes Aviel-Ronen, et al. Modern Pathology. 2008. Tumor targeting: GPC3 (oncofetal antigen)
Slide 31: BOXR1030: In Vivo Models Show Improved Activity
BOXR1030: In Vivo Models Show Improved Activity CAR-T lose activity in low glucose 2 intratumoral glucose (mM) Cancer cells deplete TME glucose 1 CAR-T active in high glucose xenografts 3 CAR-T fails in more stringent xenografts; BOXRs retain functionality 4 untreated GPC3 CAR untreated GPC3 CAR BOX
Slide 32: BOXR Pipeline
BOXR Pipeline Initiating preclinical development for BOXR1030 Additional discovery-stage BOXR programs consist of multiple leads targeting alternative mechanisms BOXR TME Mechanism Indications Target BOXR1030 Metabolic Competition Lung (SqCC) Liver (HCC) GPC3 BOXR637 BOXR889 BOXR1011 Immune cell sup
Slide 33: Business Considerations
Business consiigrationss de A.
Slide 34: Building for Commercialization
Building for Commercialization Unum uses the CliniMACS Prodigy in GMP manufacturing with centralized manufacture at a commercial CMO to support current early phase trials Enables an automated operation and closed processing of all manufacturing steps ACTR successfully manufactured for all subjects t
Slide 35: Strong Financial Position, Capital Efficient Business Model
Strong Financial Position, Capital Efficient Business Model In April 2018, completed an IPO and concurrent private placement, raising $77M in gross proceeds $154M raised since inception Strategic collaboration with Seattle Genetics has provided an additional ∼$37MM to date in non-dilutive funding Cu
Slide 36: SGEN Collaboration Exemplifies Partnering Strategy
SGEN Collaboration Exemplifies Partnering Strategy Partnership to co-develop and co-commercialize novel ACTR + SGEN mAb combination therapies Structured to leverage each partner’s expertise Collaboration provides Unum with: Access to SGEN proprietary mAbs targeting hematologic and solid tumor indica
Slide 37: 2019 Milestones
2019 Milestones NHL ACTR707 + rituximab ATTCK-20-03: dose escalation completed ATTCK-20-03: preliminary data from cohort expansion ACTR087 + rituximab ATTCK-20-2: confirm recommended Ph2 dose (study completion) Multiple Myeloma ACTR087 + SEA-BCMA ATTCK-17-01: multiple readouts from dose escalation S
Slide 38: Experienced Leadership
Experienced Leadership Geoff Hodge Chief Technical Officer Xcellerex, VP Process Development & Manufacturing GE Healthcare, Millennium Seth Ettenberg, PhD Chief Scientific Officer Novartis, Head of Oncology Biologics CuraGen, NCI Michael Vasconcelles, MD Chief Medical Officer Takeda/Millennium, Glob
Slide 39: Key Company Highlights
Key Company Highlights NOVEL, UNIVERSAL ACTR platform for cancer cell therapy 1 Promising ANTI-TUMOR ACTIVITY and FAVORABLE TOLERABILITY PROFILE 2 BROAD PIPELINE with three current clinical stage programs growing to four by 2019 3 Ability to expand pipeline RAPIDLY and COST EFFECTIVELY 4 EXPERIENCED
Unum Therapeutics — Investor Presentation (January 2019) on 6ix