UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of The Securities Exchange Act of 1934
Date of Report (Date of Earliest Event Reported): March 7, 2019
UNUM THERAPEUTICS INC.
(Exact name of registrant as specified in its charter)
| Delaware | 001-38443 | 46-5308248 | ||
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(I.R.S. Employer Identification No.) | ||
| 200 Cambridge Park Drive, Suite 3100 Cambridge, Massachusetts |
02140 | |||
| (Address of principal executive offices) | (Zip Code) | |||
Registrant’s telephone number, including area code (617) 945-5576
Not Applicable
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or Rule 12b-2 of the Securities Exchange Act of 1934.
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒
| Item 7.01 | Regulation FD Disclosure. |
Unum Therapeutics Inc. (the “Company”) is furnishing a corporate presentation, attached as Exhibit 99.1 to this Current Report on Form 8-K, which the Company intends to use from time to time in meetings with investors. The corporate presentation will also be available in the investor relations section of the Company’s website at http://unumrx.com.
The information in this Item 7.01 and Exhibit 99.1 attached hereto shall not be deemed “filed” for purposes of Section 18 of the Securities and Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section, nor shall they be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, except as expressly set forth by specific reference in such filing.
| Item 9.01 | Financial Statements and Exhibits |
| Exhibit No. |
Description | |
| 99.1 | Unum Therapeutics Inc. corporate presentation. | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: March 7, 2019 | UNUM THERAPEUTICS INC. | |||
| By: | /s/ Charles Wilson | |||
| Charles Wilson, Ph.D. | ||||
| Chief Executive Officer | ||||
Exhibit 99.1 UNUM THERAPEUTICS CORPORATE PRESENTATION TH COWEN AND COMPANY 39 ANNUAL HEALTHCARE CONFERENCE BOSTON, MA MARCH 2019Exhibit 99.1 UNUM THERAPEUTICS CORPORATE PRESENTATION TH COWEN AND COMPANY 39 ANNUAL HEALTHCARE CONFERENCE BOSTON, MA MARCH 2019
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 materially from those expressed or implied by such forward looking statements. All statements other than statements of historical fact could be deemed forward-looking, including, but not limited to, any statements of the plans, strategies, and objectives of management for future operations, including our clinical development and commercialization plans; any projections of financial information; any statement about historical results that may suggest trends for our business; any statement of expectation or belief regarding future events; potential markets or market size, technology developments, our clinical product pipeline, clinical data or the implications thereof, enforceability of our intellectual property rights, competitive strengths or our position within the industry; any statements regarding the anticipated benefits of our collaborations or other strategic transactions; and any statements of assumptions underlying any of the items mentioned. These statement are based on estimates and information available to us at the time of this presentation and are not guarantees of future performance. Actual results could differ materially from our current expectations as a result of many risks and uncertainties, including but not limited to, risks associated with: the success, cost and timing of our product development activities and clinical trials; our ability to obtain regulatory approval for and to commercialize our product candidates; our ability to establish a commercially-viable manufacturing process and manufacturing infrastructure; regulatory requirements and regulatory developments; the effects of competition and technological advances; our dependence on third-party collaborators and other contractors in our research and development activities, including for the conduct of clinical trials and the manufacture of our product candidates; our ability to obtain, maintain, or protect intellectual property rights related to our product candidates; among others. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to our business in general, see our periodic filings filed from time to time with the Securities and Exchange Commission. Unless as required by law, we assume no obligation and do not intend to update these forward looking statements or to conform these statements to actual results or to changes in our expectations. All of Unum Therapeutics (“Unum”) product candidates are investigational product candidates and their safety and efficacy have not yet been established. Unum has not obtained marketing approval for any product, and there is no certainty that any marketing approvals will be obtained or as to the timelines on which they will be obtained. Any data pertaining to Unum product candidates is interim data, and may include investigator-reported interim data for which Unum has not yet independently reviewed the source data. The interim data may not be representative of the final results that may be obtained in the corresponding trials and results from earlier trials may not be representative of results obtained in later trial or pivotal trials. PAGE 2FORWARD-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 materially from those expressed or implied by such forward looking statements. All statements other than statements of historical fact could be deemed forward-looking, including, but not limited to, any statements of the plans, strategies, and objectives of management for future operations, including our clinical development and commercialization plans; any projections of financial information; any statement about historical results that may suggest trends for our business; any statement of expectation or belief regarding future events; potential markets or market size, technology developments, our clinical product pipeline, clinical data or the implications thereof, enforceability of our intellectual property rights, competitive strengths or our position within the industry; any statements regarding the anticipated benefits of our collaborations or other strategic transactions; and any statements of assumptions underlying any of the items mentioned. These statement are based on estimates and information available to us at the time of this presentation and are not guarantees of future performance. Actual results could differ materially from our current expectations as a result of many risks and uncertainties, including but not limited to, risks associated with: the success, cost and timing of our product development activities and clinical trials; our ability to obtain regulatory approval for and to commercialize our product candidates; our ability to establish a commercially-viable manufacturing process and manufacturing infrastructure; regulatory requirements and regulatory developments; the effects of competition and technological advances; our dependence on third-party collaborators and other contractors in our research and development activities, including for the conduct of clinical trials and the manufacture of our product candidates; our ability to obtain, maintain, or protect intellectual property rights related to our product candidates; among others. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to our business in general, see our periodic filings filed from time to time with the Securities and Exchange Commission. Unless as required by law, we assume no obligation and do not intend to update these forward looking statements or to conform these statements to actual results or to changes in our expectations. All of Unum Therapeutics (“Unum”) product candidates are investigational product candidates and their safety and efficacy have not yet been established. Unum has not obtained marketing approval for any product, and there is no certainty that any marketing approvals will be obtained or as to the timelines on which they will be obtained. Any data pertaining to Unum product candidates is interim data, and may include investigator-reported interim data for which Unum has not yet independently reviewed the source data. The interim data may not be representative of the final results that may be obtained in the corresponding trials and results from earlier trials may not be representative of results obtained in later trial or pivotal trials. PAGE 2
KEY COMPANY HIGHLIGHTS Providing potentially curative T cell therapies to treat a broad range of cancer patients NOVEL TECHNOLOGIES to overcome limitations of current T cell therapies 1 Potent ANTI-TUMOR ACTIVITY and ENCOURAGING SAFETY in lead program 2 Ability to address challenges in treating SOLID TUMORS 3 MULTIPLE MILESTONES with readouts from four clinical trials in 2019 4 PAGE 3KEY COMPANY HIGHLIGHTS Providing potentially curative T cell therapies to treat a broad range of cancer patients NOVEL TECHNOLOGIES to overcome limitations of current T cell therapies 1 Potent ANTI-TUMOR ACTIVITY and ENCOURAGING SAFETY in lead program 2 Ability to address challenges in treating SOLID TUMORS 3 MULTIPLE MILESTONES with readouts from four clinical trials in 2019 4 PAGE 3
CURRENT CHALLENGES FOR T CELL THERAPIES CAR-T therapy liabilities limit their use in broad patient populations n CRS and/or neurotoxicity are observed in the majority of patients who are treated Severe toxicities with currently approved CAR-T therapies, and can be severe or life-threatening associated with n These toxicities limit the patient population fit for CAR-T therapy, create T cell activation unpredictable risks to patients and unnecessary burden on the healthcare system n Traditional CAR-T cannot discriminate between high level expression of antigen on Limited ability to tumor cells versus low level expression on healthy tissue target solid tumor n Several CAR-Ts have shown toxicities consistent with on-target – off-tumor toxicity antigens (e.g., CAIX, HER2) n The microenvironments of many solid tumors inhibit immune function limiting Lack of efficacy in efficacy of engineered T cells solid tumors due to n CAR-T therapies to date have not demonstrated potent efficacy in solid tumors immunosuppression PAGE 4CURRENT CHALLENGES FOR T CELL THERAPIES CAR-T therapy liabilities limit their use in broad patient populations n CRS and/or neurotoxicity are observed in the majority of patients who are treated Severe toxicities with currently approved CAR-T therapies, and can be severe or life-threatening associated with n These toxicities limit the patient population fit for CAR-T therapy, create T cell activation unpredictable risks to patients and unnecessary burden on the healthcare system n Traditional CAR-T cannot discriminate between high level expression of antigen on Limited ability to tumor cells versus low level expression on healthy tissue target solid tumor n Several CAR-Ts have shown toxicities consistent with on-target – off-tumor toxicity antigens (e.g., CAIX, HER2) n The microenvironments of many solid tumors inhibit immune function limiting Lack of efficacy in efficacy of engineered T cells solid tumors due to n CAR-T therapies to date have not demonstrated potent efficacy in solid tumors immunosuppression PAGE 4
ACTR: ANTIBODY-COUPLED T CELL RECEPTOR An engineered T cell receptor that uses tumor-targeting mAbs to direct attack Potential ACTR benefits tumor-specific antibody § The same universal T cell product can be ACTR antigen used in several different cancer indications n Potent anti-tumor activity with reduced rates and severities of CAR-T associated toxicities n Ability to pursue antigens inaccessible to CAR-T n Selectively target solid tumor antigens, avoiding on-target off-tumor toxicity ACTR T cell tumor cell n Target T cell-expressed antigens, avoiding fratricide ACTR components § antibody recognition: ectodomain of CD16 (normally found on NK cells), linked via a hinge and transmembrane domain § T cell activation: costimulatory signals (e.g., CD28 or 41BB) and TCR signals (CD3!) PAGE 5ACTR: ANTIBODY-COUPLED T CELL RECEPTOR An engineered T cell receptor that uses tumor-targeting mAbs to direct attack Potential ACTR benefits tumor-specific antibody § The same universal T cell product can be ACTR antigen used in several different cancer indications n Potent anti-tumor activity with reduced rates and severities of CAR-T associated toxicities n Ability to pursue antigens inaccessible to CAR-T n Selectively target solid tumor antigens, avoiding on-target off-tumor toxicity ACTR T cell tumor cell n Target T cell-expressed antigens, avoiding fratricide ACTR components § antibody recognition: ectodomain of CD16 (normally found on NK cells), linked via a hinge and transmembrane domain § T cell activation: costimulatory signals (e.g., CD28 or 41BB) and TCR signals (CD3!) PAGE 5
BOXR: BOLT-ON CHIMERIC RECEPTOR Designed to improve T cell function in solid tumor microenvironments Potential BOXR benefits chimeric receptor ‘bolt-on’ (ACTR or CAR) transgene § T cell function improved by expression of a immunosuppressive cells ‘bolt-on’ transgene (e.g., metabolic (Treg, MDSC) enzymes/transporters, signaling receptors/ligands, survival factors, etc.) BOXR T cell § Counteracts mechanisms driving secreted factors immunosuppression in solid tumors metabolites § Metabolic competition § Immune cell suppression (T-Reg, MDSC) § Chronic antigen stimulation tumor cells § Bolt-on transgene may augment many types BOXR components of T cell therapies (ACTR, CAR, TCR, TIL, etc.) § chimeric receptor: universal ACTR or antigen-specific CAR drives cancer cell targeting and attack § bolt-on: novel transgene re-programs T cell biology to improve functionality in the tumor microenvironment PAGE 6BOXR: BOLT-ON CHIMERIC RECEPTOR Designed to improve T cell function in solid tumor microenvironments Potential BOXR benefits chimeric receptor ‘bolt-on’ (ACTR or CAR) transgene § T cell function improved by expression of a immunosuppressive cells ‘bolt-on’ transgene (e.g., metabolic (Treg, MDSC) enzymes/transporters, signaling receptors/ligands, survival factors, etc.) BOXR T cell § Counteracts mechanisms driving secreted factors immunosuppression in solid tumors metabolites § Metabolic competition § Immune cell suppression (T-Reg, MDSC) § Chronic antigen stimulation tumor cells § Bolt-on transgene may augment many types BOXR components of T cell therapies (ACTR, CAR, TCR, TIL, etc.) § chimeric receptor: universal ACTR or antigen-specific CAR drives cancer cell targeting and attack § bolt-on: novel transgene re-programs T cell biology to improve functionality in the tumor microenvironment PAGE 6
PIPELINE Rapidly expanding pipeline in both hematologic and solid tumor cancers Product Candidate Indication Antibody Pre-Clinical Phase I Hematologic Cancers ACTR707 r/r CD20+ B cell NHL rituximab ATTCK-20-03 ACTR087 r/r CD20+ B cell NHL rituximab ATTCK-20-2 SEA-BCMA ACTR087 r/r Multiple Myeloma ATTCK-17-01 with Seattle Genetics Solid Tumor Cancers ACTR707 Advanced HER2+ cancers trastuzumab ATTCK-34-01 BOXR1030 Advanced GPC3+ cancers n/a ACTR087 and ACTR707 distinguished by differences in co-stimulatory domains (ACTR087: 4-1BB, ACTR707: CD28) and structural sequences PAGE 7PIPELINE Rapidly expanding pipeline in both hematologic and solid tumor cancers Product Candidate Indication Antibody Pre-Clinical Phase I Hematologic Cancers ACTR707 r/r CD20+ B cell NHL rituximab ATTCK-20-03 ACTR087 r/r CD20+ B cell NHL rituximab ATTCK-20-2 SEA-BCMA ACTR087 r/r Multiple Myeloma ATTCK-17-01 with Seattle Genetics Solid Tumor Cancers ACTR707 Advanced HER2+ cancers trastuzumab ATTCK-34-01 BOXR1030 Advanced GPC3+ cancers n/a ACTR087 and ACTR707 distinguished by differences in co-stimulatory domains (ACTR087: 4-1BB, ACTR707: CD28) and structural sequences PAGE 7
HEMATOLOGIC CANCERSHEMATOLOGIC CANCERS
ACTR IN LYMPHOMA Provides proof-of-platform for the ACTR technology, demonstrating potential best-in-class product profile § Compelling profile demonstrated at early dose levels in two independent trials in r/r NHL § ATTCK-20-03: ACTR707 (CD28) (selected as program lead) § ATTCK-20-2: ACTR087 (41BB) § Anti-tumor activity comparable to approved NHL CAR-T therapies § Favorable safety demonstrated at the correct dose level § Potential profile opens path for applying T cell therapies across broad NHL patient populations including those unfit for current CAR-T PAGE 9ACTR IN LYMPHOMA Provides proof-of-platform for the ACTR technology, demonstrating potential best-in-class product profile § Compelling profile demonstrated at early dose levels in two independent trials in r/r NHL § ATTCK-20-03: ACTR707 (CD28) (selected as program lead) § ATTCK-20-2: ACTR087 (41BB) § Anti-tumor activity comparable to approved NHL CAR-T therapies § Favorable safety demonstrated at the correct dose level § Potential profile opens path for applying T cell therapies across broad NHL patient populations including those unfit for current CAR-T PAGE 9
TESTING ACTR707 IN NHL Study Design and Objectives § Phase I, single arm trial testing escalating single doses of ACTR+ T cells in combination with rituximab § Patients pretreated with 3 days of lymphodepleting chemotherapy (fludarabine + cytarabine) 2 § Rituximab administered on the R-CHOP schedule (375 mg/m IV every 3-weeks) § Key Eligibility: Rituximab-treated CD20+ aggressive NHL; Primary refractory, >2 prior lines of therapy, or post auto-HSCT § Primary objective is safety, determination of MTD and proposed recommended Phase II dose Status ATTCK-20-03 Trial Design § 14 patients dosed to date through first three dose cohorts Dose Escalation* § Cleared DLT assessment at DL3, Expansion completing response assessments § Enrolling patients at DL4 Cohort 1, n = 6 Cohort 2, n = 3 Cohort 3, n = 5 Cohort 4, n = 3-6 n = 26 Next Steps 25M Cells 40M Cells 55M Cells RP2D (TBD) 80M Cells § Complete dose escalation, safety evaluation and response assessments currently enrolling § Cohort expansion at recommended phase 2 dose (RP2D) *study design allows for additional dose cohorts PAGE 10TESTING ACTR707 IN NHL Study Design and Objectives § Phase I, single arm trial testing escalating single doses of ACTR+ T cells in combination with rituximab § Patients pretreated with 3 days of lymphodepleting chemotherapy (fludarabine + cytarabine) 2 § Rituximab administered on the R-CHOP schedule (375 mg/m IV every 3-weeks) § Key Eligibility: Rituximab-treated CD20+ aggressive NHL; Primary refractory, >2 prior lines of therapy, or post auto-HSCT § Primary objective is safety, determination of MTD and proposed recommended Phase II dose Status ATTCK-20-03 Trial Design § 14 patients dosed to date through first three dose cohorts Dose Escalation* § Cleared DLT assessment at DL3, Expansion completing response assessments § Enrolling patients at DL4 Cohort 1, n = 6 Cohort 2, n = 3 Cohort 3, n = 5 Cohort 4, n = 3-6 n = 26 Next Steps 25M Cells 40M Cells 55M Cells RP2D (TBD) 80M Cells § Complete dose escalation, safety evaluation and response assessments currently enrolling § Cohort expansion at recommended phase 2 dose (RP2D) *study design allows for additional dose cohorts PAGE 10
ACTR707 TOLERABILITY IN NHL No DLTs and no significant CRS or neurologic events in the first two dose levels Subjects with Serious Adverse Events (SAEs) Related to ACTR707 Preferred Term, n (%) Dose Level 1 (n=6) Dose Level 2 (n=3) Febrile neutropenia 1 (17) 1 (33) Pancytopenia 0 (0) 1 (33) Subjects with AESI, n Adverse Events of Special Interest (AESI) Dose Level 1 Dose Level 2 (n=6) (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 Clinically significant rheumatologic/autoimmune disorder 0 0 Clinically significant hematologic disorder (excluding cytopenias related to LD chemo) 0 0 Clinically significant = in the opinion of the investigator, clinically meaningful Database snapshot: 01November18 PAGE 11ACTR707 TOLERABILITY IN NHL No DLTs and no significant CRS or neurologic events in the first two dose levels Subjects with Serious Adverse Events (SAEs) Related to ACTR707 Preferred Term, n (%) Dose Level 1 (n=6) Dose Level 2 (n=3) Febrile neutropenia 1 (17) 1 (33) Pancytopenia 0 (0) 1 (33) Subjects with AESI, n Adverse Events of Special Interest (AESI) Dose Level 1 Dose Level 2 (n=6) (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 Clinically significant rheumatologic/autoimmune disorder 0 0 Clinically significant hematologic disorder (excluding cytopenias related to LD chemo) 0 0 Clinically significant = in the opinion of the investigator, clinically meaningful Database snapshot: 01November18 PAGE 11
ACTR707 ANTI-TUMOR ACTIVITY IN NHL Potent antitumor activity including complete responses in initial cohorts Dose Level 1 § Six enrolled and treated subjects § Three subjects with complete responses; three with disease progression Dose Level 2 § Three enrolled and treated subjects § One subject with complete response; two with disease progression Summary of complete responses # prior Refractory* to Dose Level Response Diagnosis therapies^ prior therapy 1 Complete 2 no Gr3b FL 1 Complete 5 yes DLBCL Baseline Cycle 3 1 Complete 3 yes DLBCL Representative image of complete response in DLBCL subject treated with 5 prior therapies including ASCT 2 Complete 3 yes DLBCL *Refractory defined as PD as best response to any line of prior therapy or relapse ≤ 12 months post ASCT ^All subjects received rituximab as prior therapy Database snapshot: 01November18 PAGE 12ACTR707 ANTI-TUMOR ACTIVITY IN NHL Potent antitumor activity including complete responses in initial cohorts Dose Level 1 § Six enrolled and treated subjects § Three subjects with complete responses; three with disease progression Dose Level 2 § Three enrolled and treated subjects § One subject with complete response; two with disease progression Summary of complete responses # prior Refractory* to Dose Level Response Diagnosis therapies^ prior therapy 1 Complete 2 no Gr3b FL 1 Complete 5 yes DLBCL Baseline Cycle 3 1 Complete 3 yes DLBCL Representative image of complete response in DLBCL subject treated with 5 prior therapies including ASCT 2 Complete 3 yes DLBCL *Refractory defined as PD as best response to any line of prior therapy or relapse ≤ 12 months post ASCT ^All subjects received rituximab as prior therapy Database snapshot: 01November18 PAGE 12
CD19 CAR-T BENCHMARK IN NHL Initial data indicates potential for a durable CR rate in line with approved CD19 CAR-T with an improved safety profile YESCARTA® KYMRIAH® (axicabtagene ciloleucel) (tisagenlecleucel) Indication r/r DLBCL, PMBCL, TFL r/r DLBCL N evaluable for response 101 68 OR rate 72% 50% CR rate 51% 32% a b Ongoing OR at 6 months 44% 33% a b Ongoing CR at 6 months 39% 29% N evaluable for safety 108 106 CRS (≥Grade 3) 94% (13%) 74% (23%) Neurologic toxicities (≥Grade 3) 87% (31%) 58% (18%) No head to head trials have been conducted that would enable a direct safety and efficacy comparison to Yescarta or Kymriah Source: USPI unless otherwise noted a AACR, 2017. Analysis triggered when 92 patients reached a minimum of 6 months followup. b Schuster, SJ et. al. NEJM 2019. Analysis based on 93 subjects who received tisagenlecleucel in the JULIET study. PAGE 13CD19 CAR-T BENCHMARK IN NHL Initial data indicates potential for a durable CR rate in line with approved CD19 CAR-T with an improved safety profile YESCARTA® KYMRIAH® (axicabtagene ciloleucel) (tisagenlecleucel) Indication r/r DLBCL, PMBCL, TFL r/r DLBCL N evaluable for response 101 68 OR rate 72% 50% CR rate 51% 32% a b Ongoing OR at 6 months 44% 33% a b Ongoing CR at 6 months 39% 29% N evaluable for safety 108 106 CRS (≥Grade 3) 94% (13%) 74% (23%) Neurologic toxicities (≥Grade 3) 87% (31%) 58% (18%) No head to head trials have been conducted that would enable a direct safety and efficacy comparison to Yescarta or Kymriah Source: USPI unless otherwise noted a AACR, 2017. Analysis triggered when 92 patients reached a minimum of 6 months followup. b Schuster, SJ et. al. NEJM 2019. Analysis based on 93 subjects who received tisagenlecleucel in the JULIET study. PAGE 13
PRODUCT OPPORTUNITY IN NHL Potential to address unmet medical need for under-served patient populations Comparable durable CR rate and reduced CRS/neurotox would enable several paths forward § Compete directly with approved CAR-Ts § Move more quickly into earlier lines of therapy § Expand into new patient populations r/r DLBCL Total of over 20K r/r Follicular Lymphoma patients per year Potential best-in-class profile directly competes in the US CD19 CAR-T exposed with current CAR-T Tolerability is a key differentiator in patients Profile may directly support CD19 loss/mutation are with indolent lymphomas use in earlier lines common mechanisms of relapse to CD19 CAR-T, and not all patients derive benefit PAGE 14PRODUCT OPPORTUNITY IN NHL Potential to address unmet medical need for under-served patient populations Comparable durable CR rate and reduced CRS/neurotox would enable several paths forward § Compete directly with approved CAR-Ts § Move more quickly into earlier lines of therapy § Expand into new patient populations r/r DLBCL Total of over 20K r/r Follicular Lymphoma patients per year Potential best-in-class profile directly competes in the US CD19 CAR-T exposed with current CAR-T Tolerability is a key differentiator in patients Profile may directly support CD19 loss/mutation are with indolent lymphomas use in earlier lines common mechanisms of relapse to CD19 CAR-T, and not all patients derive benefit PAGE 14
ACTR IN MULTIPLE MYELOMA Multiple mechanisms of action of ACTR in combination with SEA-BCMA enable a potentially more effective treatment compared to BCMA-targeting CAR-T APRIL signaling blockade 2 Potential differentiating characteristics myeloma cell APRIL BCMA § Despite high response rates, durability remains ACTR T cell a concern for many BCMA-targeted programs ACTR in development SEA-BCMA § Improved ACTR T cell persistence may translate into enhanced response duration CD16 NK cell § Three mechanisms of action combine to potentially counteract resistance mechanisms and enhance durability: ACTR T cell killing 1 § BCMA-targeted T cell cytotoxicity § APRIL-signaling blockade § NK cell-mediated ADCC Classical ADCC (via NK cell) 3 PAGE 15ACTR IN MULTIPLE MYELOMA Multiple mechanisms of action of ACTR in combination with SEA-BCMA enable a potentially more effective treatment compared to BCMA-targeting CAR-T APRIL signaling blockade 2 Potential differentiating characteristics myeloma cell APRIL BCMA § Despite high response rates, durability remains ACTR T cell a concern for many BCMA-targeted programs ACTR in development SEA-BCMA § Improved ACTR T cell persistence may translate into enhanced response duration CD16 NK cell § Three mechanisms of action combine to potentially counteract resistance mechanisms and enhance durability: ACTR T cell killing 1 § BCMA-targeted T cell cytotoxicity § APRIL-signaling blockade § NK cell-mediated ADCC Classical ADCC (via NK cell) 3 PAGE 15
TESTING ACTR087 IN MULTIPLE MYELOMA Promising safety profile through early dose cohorts supports further dose escalation Study Design and Objectives § Phase I, single arm trial testing escalating single doses of ACTR+ T cells in combination with escalating SEA-BCMA § Patients pretreated with 3 days of lymphodepleting chemotherapy (fludarabine + cytarabine) § Antibody administered on a 3-week cycle § Key Eligibility: r/r multiple myeloma, ≥3 prior lines of therapy or double refractory § Primary objective is safety, tolerability and to determine recommended Phase II dose Additional cohorts ATTCK-17-01 Trial Design Status at higher Ab and/or cell doses § Three dose levels completed at very low Cohort 2, n=1 antibody doses and 30M ACTR+ T cells Cohort 5b, n = 3-6 0.1 mg/kg Ab Potential increase § No dose limiting toxicities observed 2.0 mg/kg Ab in cell dose Cohort 1, n=1 § No severe CRS or neurologic events observed 0.03 mg/kg Ab Cohort 3, n = 5 Cohort 4, n = 3-6 Cohort 5a, n = 3-6 Next Steps 2.0 mg/kg Ab 5.0 mg/kg Ab § Continuation of dose escalation exploring 0.3 mg/kg Ab increases in cell and/or Ab dose currently active PAGE 16TESTING ACTR087 IN MULTIPLE MYELOMA Promising safety profile through early dose cohorts supports further dose escalation Study Design and Objectives § Phase I, single arm trial testing escalating single doses of ACTR+ T cells in combination with escalating SEA-BCMA § Patients pretreated with 3 days of lymphodepleting chemotherapy (fludarabine + cytarabine) § Antibody administered on a 3-week cycle § Key Eligibility: r/r multiple myeloma, ≥3 prior lines of therapy or double refractory § Primary objective is safety, tolerability and to determine recommended Phase II dose Additional cohorts ATTCK-17-01 Trial Design Status at higher Ab and/or cell doses § Three dose levels completed at very low Cohort 2, n=1 antibody doses and 30M ACTR+ T cells Cohort 5b, n = 3-6 0.1 mg/kg Ab Potential increase § No dose limiting toxicities observed 2.0 mg/kg Ab in cell dose Cohort 1, n=1 § No severe CRS or neurologic events observed 0.03 mg/kg Ab Cohort 3, n = 5 Cohort 4, n = 3-6 Cohort 5a, n = 3-6 Next Steps 2.0 mg/kg Ab 5.0 mg/kg Ab § Continuation of dose escalation exploring 0.3 mg/kg Ab increases in cell and/or Ab dose currently active PAGE 16
SOLID TUMOR CANCERSSOLID TUMOR CANCERS
ACTR + TRASTUZUMAB IN HER2+ TUMORS First ACTR solid tumor program tumor cell lines normal tissue cells § Combination for the treatment of adult patients with (HER2 high) (HER2 low) relapsed/refractory advanced HER2+ cancers § Enrolling patients with HER2+ breast cancer, gastric cancers, and other HER2+ malignancies HER2 is a challenging target for traditional CAR-T § Like many solid tumor antigens, HER2 is expressed at low levels on some normal tissues § Several CAR-T have shown toxicities consistent with on-target-off-tumor toxicity (e.g., CAIX, HER2) § Preclinical studies demonstrate a threshold effect for ACTR cytotoxic killing – minimal activity when antigen ACTR + is below a target threshold trastuzumab HER2 CAR PAGE 18ACTR + TRASTUZUMAB IN HER2+ TUMORS First ACTR solid tumor program tumor cell lines normal tissue cells § Combination for the treatment of adult patients with (HER2 high) (HER2 low) relapsed/refractory advanced HER2+ cancers § Enrolling patients with HER2+ breast cancer, gastric cancers, and other HER2+ malignancies HER2 is a challenging target for traditional CAR-T § Like many solid tumor antigens, HER2 is expressed at low levels on some normal tissues § Several CAR-T have shown toxicities consistent with on-target-off-tumor toxicity (e.g., CAIX, HER2) § Preclinical studies demonstrate a threshold effect for ACTR cytotoxic killing – minimal activity when antigen ACTR + is below a target threshold trastuzumab HER2 CAR PAGE 18
TESTING ACTR707 IN HER2+ SOLID TUMORS Study Design & Objectives § Open label Phase I adaptive dose-escalating study to define optimal ACTR cell dose and antibody dose § Key eligibility: Advanced HER2 (3+) solid tumor malignancy. Must have received adequate prior therapy including HER2 directed therapy § Primary objectives: assess safety, tolerability, and to determine recommended Phase II dose ATTCK-34-01 Trial Design Status Expansion Dose Escalation* § Currently enrolling patients in Cohort 1 § Completing additional site activations Cohort 2b, n=3-6 Cohort 3, n=3-6 ^ # Next Steps 1.0 mg/kg Ab 2.0 mg/kg Ab 40M Cells 40M Cells § Proceed with dose escalation through 2019 n=36 § Potential for multiple expansion cohorts RP2D Cohort 1, n=3-6 Cohort 2a, n=3-6 across specific HER2+ malignancies ^ # 1.0 mg/kg Ab 2.0 mg/kg Ab 25M Cells 25M Cells *study design has the flexibility to modify or add additional cohorts ^ 1 mg/kg weekly X 6wks then 3 mg/kg q3w # 2 mg/kg weekly X 6wks then 6 mg/kg q3w currently enrolling PAGE 19TESTING ACTR707 IN HER2+ SOLID TUMORS Study Design & Objectives § Open label Phase I adaptive dose-escalating study to define optimal ACTR cell dose and antibody dose § Key eligibility: Advanced HER2 (3+) solid tumor malignancy. Must have received adequate prior therapy including HER2 directed therapy § Primary objectives: assess safety, tolerability, and to determine recommended Phase II dose ATTCK-34-01 Trial Design Status Expansion Dose Escalation* § Currently enrolling patients in Cohort 1 § Completing additional site activations Cohort 2b, n=3-6 Cohort 3, n=3-6 ^ # Next Steps 1.0 mg/kg Ab 2.0 mg/kg Ab 40M Cells 40M Cells § Proceed with dose escalation through 2019 n=36 § Potential for multiple expansion cohorts RP2D Cohort 1, n=3-6 Cohort 2a, n=3-6 across specific HER2+ malignancies ^ # 1.0 mg/kg Ab 2.0 mg/kg Ab 25M Cells 25M Cells *study design has the flexibility to modify or add additional cohorts ^ 1 mg/kg weekly X 6wks then 3 mg/kg q3w # 2 mg/kg weekly X 6wks then 6 mg/kg q3w currently enrolling PAGE 19
IL-2 PGE 2 Prolif IL-2 Adenosine Prolif IL-2 Kynurenine Prolif Prolif TGF-b Prolif BOXR DISCOVERY ENGINE Enables discovery of ACTR- and CAR-based BOXR candidates Score addressing specific mechanisms of immunosuppression BOXR Discovery Engine Translational Medicine Biologic Hypothesis ACTR parent Identify patients whose Unique insights into tumors are most immunoregulation within susceptible to each BOXR tumors High Throughput In Vivo Validation Screening Stringent xenograft models Novel, multi-stage to test BOXR activity in screening strategy to hostile environments simulate TME Anderson et al., Cancer Cell, 31:311-325 (2017) PAGE 20 BOXR constructsIL-2 PGE 2 Prolif IL-2 Adenosine Prolif IL-2 Kynurenine Prolif Prolif TGF-b Prolif BOXR DISCOVERY ENGINE Enables discovery of ACTR- and CAR-based BOXR candidates Score addressing specific mechanisms of immunosuppression BOXR Discovery Engine Translational Medicine Biologic Hypothesis ACTR parent Identify patients whose Unique insights into tumors are most immunoregulation within susceptible to each BOXR tumors High Throughput In Vivo Validation Screening Stringent xenograft models Novel, multi-stage to test BOXR activity in screening strategy to hostile environments simulate TME Anderson et al., Cancer Cell, 31:311-325 (2017) PAGE 20 BOXR constructs
BOXR1030: FIRST BOXR CANDIDATE BOXR1030 is a GPC3 targeted CAR-T engineered for enhanced metabolism in the solid tumor microenvironment 20 Stringent xenograft models deplete TME glucose § Low glucose compromises T cell function, correlates with poor 15 patient outcomes in lung and liver cancers 10 § BOXR1030 has superior activity in xenograft models that mimic the low glucose environments of lung and liver tumors 5 mM 5 0 BOXR1030 GPC3 CAR BOXR1030 activity in low glucose HEP3B model GPC3 ‘bolt-on’ 1500 CAR transgene untreated 1000 GPC3 CAR bolt-on enzyme that improves T-cell metabolism 500 BOXR1030 0 0 20 40 60 80 100 Time (Day) PAGE 21 Blood (tail) HepG2 NCI-H446 Hep3B JHH7 3 Intratumoral glucose Tumor volume (mm ) Glucose (mM) (mM)BOXR1030: FIRST BOXR CANDIDATE BOXR1030 is a GPC3 targeted CAR-T engineered for enhanced metabolism in the solid tumor microenvironment 20 Stringent xenograft models deplete TME glucose § Low glucose compromises T cell function, correlates with poor 15 patient outcomes in lung and liver cancers 10 § BOXR1030 has superior activity in xenograft models that mimic the low glucose environments of lung and liver tumors 5 mM 5 0 BOXR1030 GPC3 CAR BOXR1030 activity in low glucose HEP3B model GPC3 ‘bolt-on’ 1500 CAR transgene untreated 1000 GPC3 CAR bolt-on enzyme that improves T-cell metabolism 500 BOXR1030 0 0 20 40 60 80 100 Time (Day) PAGE 21 Blood (tail) HepG2 NCI-H446 Hep3B JHH7 3 Intratumoral glucose Tumor volume (mm ) Glucose (mM) (mM)
SOLID TUMOR PRECLINICAL PIPELINE Multiple platform technologies (ACTR and BOXR) enable a broad pipeline tailored to particular targets and tumor types ACTR-targeted BOXR overcomes immune cell suppression MDSCs Tregs BOXR parent MDSCs Tregs Tumor Targeting Technology: Either ACTR BOXR parent 100 BOXR637 100 or CAR depending on factors including: BOXR637 75 § potential for off-tumor attack 75 MDSCs: 50 § antibody availability Myeloid-Derived MDSCs: 50 Suppressor Cells Myeloid-Derived 25 Suppressor Cells Tregs: 25 mAb Regulatory T cells Tregs: 0 scFv Regulatory T cells 0 Proliferation IF IFN- N-γ! proliferation Proliferation IFN-γ CAR-targeted BOXR overcomes exhaustion / chronic stimulation 6 BOXR parent ACTR CAR BOXR947 4 Bolt-on Technology: Tailored to different BOXR950 indications based upon translational BOXR951 insights 2 0 PAGE 22 Response (% non-suppressed) 3rd round proliferation Response response proliferation following (fold change) (% non-suppressed) (%non-suppressed) restimulation (-fold)SOLID TUMOR PRECLINICAL PIPELINE Multiple platform technologies (ACTR and BOXR) enable a broad pipeline tailored to particular targets and tumor types ACTR-targeted BOXR overcomes immune cell suppression MDSCs Tregs BOXR parent MDSCs Tregs Tumor Targeting Technology: Either ACTR BOXR parent 100 BOXR637 100 or CAR depending on factors including: BOXR637 75 § potential for off-tumor attack 75 MDSCs: 50 § antibody availability Myeloid-Derived MDSCs: 50 Suppressor Cells Myeloid-Derived 25 Suppressor Cells Tregs: 25 mAb Regulatory T cells Tregs: 0 scFv Regulatory T cells 0 Proliferation IF IFN- N-γ! proliferation Proliferation IFN-γ CAR-targeted BOXR overcomes exhaustion / chronic stimulation 6 BOXR parent ACTR CAR BOXR947 4 Bolt-on Technology: Tailored to different BOXR950 indications based upon translational BOXR951 insights 2 0 PAGE 22 Response (% non-suppressed) 3rd round proliferation Response response proliferation following (fold change) (% non-suppressed) (%non-suppressed) restimulation (-fold)
BUILDING FOR THE FUTUREBUILDING FOR THE FUTURE
PLATFORM ENHANCES COMMERCIALIZATION POTENTIAL Reduced Scalable Reliability Turn around Simplifying Patient COGS capacity time patient care access Closed automated CMO capacity 100% success Currently in line Improved safety Improved safety profile supports current with best practice profile enables system enables delivering ACTR enables expansion to development in early scalability and product to patient to reduced need for the community reduced operator activities, ability to date development monitoring and setting to access a scale with additional time; further hospitalization, broader patient Closed automated Clear opportunity suites process reducing overall population to shorten through system reduces risk automation cost and Clear path to scale accelerated for contamination Physician familiarity maximizes plant complexity of manufacturing to release testing with universal product utilization administration meet commercial accelerates adoption need in Unum owned Cost synergies of of future products manufacturing site a universal product (e.g., large scale virus manufacture) improving the patient experience optimizing economics PAGE 24PLATFORM ENHANCES COMMERCIALIZATION POTENTIAL Reduced Scalable Reliability Turn around Simplifying Patient COGS capacity time patient care access Closed automated CMO capacity 100% success Currently in line Improved safety Improved safety profile supports current with best practice profile enables system enables delivering ACTR enables expansion to development in early scalability and product to patient to reduced need for the community reduced operator activities, ability to date development monitoring and setting to access a scale with additional time; further hospitalization, broader patient Closed automated Clear opportunity suites process reducing overall population to shorten through system reduces risk automation cost and Clear path to scale accelerated for contamination Physician familiarity maximizes plant complexity of manufacturing to release testing with universal product utilization administration meet commercial accelerates adoption need in Unum owned Cost synergies of of future products manufacturing site a universal product (e.g., large scale virus manufacture) improving the patient experience optimizing economics PAGE 24
STRONG FINANCIAL POSITION Unum has a capital-efficient business model and significant funding through both financing and partnerships Finances § In April 2018, completed an IPO and concurrent private placement, raising $77M in gross proceeds § $154M raised since inception § Current cash balance of $87M (as of 09/30) provides runway through at least Q2 2020 § 9-months ended 09/30/2018 operating cash flow: ($23.5M) Seattle Genetics Partnership § Strategic collaboration with Seattle Genetics has provided an additional ∼$37MM to date in non-dilutive funding § Partnership to co-develop and co-commercialize novel ACTR + SGEN mAb combination therapies § Structured to leverage each partner’s expertise § Provides us access to SGEN proprietary mAbs with retained value and rights in programs PAGE 25STRONG FINANCIAL POSITION Unum has a capital-efficient business model and significant funding through both financing and partnerships Finances § In April 2018, completed an IPO and concurrent private placement, raising $77M in gross proceeds § $154M raised since inception § Current cash balance of $87M (as of 09/30) provides runway through at least Q2 2020 § 9-months ended 09/30/2018 operating cash flow: ($23.5M) Seattle Genetics Partnership § Strategic collaboration with Seattle Genetics has provided an additional ∼$37MM to date in non-dilutive funding § Partnership to co-develop and co-commercialize novel ACTR + SGEN mAb combination therapies § Structured to leverage each partner’s expertise § Provides us access to SGEN proprietary mAbs with retained value and rights in programs PAGE 25
UPCOMING MILESTONES Multiple readouts across programs in 2019 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 Solid tumors ACTR707 + trastuzumab ATTCK-34-01: patient dosing initiated ATTCK-34-01: dose escalation initial readouts BOXR1030 Initiate preclinical development PAGE 26UPCOMING MILESTONES Multiple readouts across programs in 2019 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 Solid tumors ACTR707 + trastuzumab ATTCK-34-01: patient dosing initiated ATTCK-34-01: dose escalation initial readouts BOXR1030 Initiate preclinical development PAGE 26
EXPERIENCED LEADERSHIP Chuck Wilson, PhD Novartis, Global Head of Strategic Alliances Archemix, Chief Technology Officer Chief Executive Officer Seth Ettenberg, PhD Novartis, Head of Oncology Biologics CuraGen, NCI Chief Scientific Officer Geoff Hodge Xcellerex, VP Process Development & Manufacturing GE Healthcare, Millennium Chief Technical Officer Michael Vasconcelles, MD Takeda/Millennium, Therapeutic Area Head of Oncology Sanofi, Genzyme Chief Medical Officer PAGE 27EXPERIENCED LEADERSHIP Chuck Wilson, PhD Novartis, Global Head of Strategic Alliances Archemix, Chief Technology Officer Chief Executive Officer Seth Ettenberg, PhD Novartis, Head of Oncology Biologics CuraGen, NCI Chief Scientific Officer Geoff Hodge Xcellerex, VP Process Development & Manufacturing GE Healthcare, Millennium Chief Technical Officer Michael Vasconcelles, MD Takeda/Millennium, Therapeutic Area Head of Oncology Sanofi, Genzyme Chief Medical Officer PAGE 27
28 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 LEADERSHIP TEAM 528 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 LEADERSHIP TEAM 5