Unum Therapeutics Reports Second Quarter 2019 Financial Results and Provides Corporate Updates
- Updated results from Phase 1 trial with ACTR707 in combination with rituximab in adults with relapsed/refractory non-Hodgkin lymphoma confirms the clinical activity achieved in previous cohorts with no adverse events of cytokine release syndrome or severe neurotoxicity –
- Phase 1 trial enrollment continuing with ACTR707 in combination with trastuzumab in HER2+ solid tumor cancers -
- IND-enabling studies underway with BOXR1030 in solid tumor cancers -
“During the quarter, we advanced our preclinical and clinical pipeline programs that are designed to improve the targeting and functionality of T cells to expand their use in hematologic and solid tumor cancers,” said
Recent Program and Corporate Highlights
ACTR707 Hematologic Program Highlights:
- Preliminary results from Cohort 3 from the Phase 1 trial (ATTCK-20-03) in non-Hodgkin lymphoma: Today,
Unumprovided preliminary results from patients treated in Cohort 3 in ATTCK-20-03, a Phase 1, multicenter, open-label, single-arm, dose-escalating trial evaluating ACTR707 in combination with rituximab in patients with relapsed/refractory CD20+ B cell non-Hodgkin lymphoma (r/r NHL) who, among other criteria, received adequate prior anti-lymphoma therapy, including anti-CD20 monoclonal antibody and chemotherapy. Among the 14 patients treated in Cohorts 1, 2 and 3, the majority (93%) were diagnosed with diffuse large B-cell lymphoma (DLBCL) and were heavily pre-treated with 57% having received three or more prior lines of therapy. Previously, results from the six patients treated in Cohort 1 (25M ACTR707+ T cells) and the three patients treated in Cohort 2 (40M ACTR707+ T cells) were presented at the American Society of Hematology(ASH) Annual Meeting in December 2018. As presented at ASH, complete responses were achieved in three of six patients (50%) from Cohort 1 and a complete response was achieved in one of three (33%) patients from Cohort 2. The overall response rate, including complete and partial responses, was 50% in Cohort 1 and 67% in Cohort 2.
As a preliminary update provided today, for the five patients treated in Cohort 3 (55M ACTR707+ T cells), a complete response was achieved in one of five patients (20%) with overall responses in four of five patients (80%). The overall responses achieved in this cohort included evidence of deepening responses in two patients whose stable disease improved after the initial response assessment at day 42 to a partial and a complete response, respectively, as of the data cutoff in
May 2019(Table 1).
|Table 1: ACTR707 Preliminary Phase 1 trial efficacy results in r/r NHL (Cohorts 1-3)|
|Clinical Response (1)||Cohort 1
|Complete Response||3||1||1||36% (5/14)|
|Partial Response||0||1||3||29% (4/14)|
|Indeterminate Response||1||0||0||7% (1/14)|
|Progressive Disease||2||1||1||29% (4/14)|
|Overall Response Rate||50% (3/6)||67% (2/3)||80% (4/5)||64% (9/14)|
|ACTR707 + T cells administered per patient (range)||25M (23-38M)||40M (30-50M)||55M (45-55M)|
|(1) Data cutoff as of May 2019|
|Durable responses were observed in patients achieving a complete response with the durability of response ranging from 85-387+ days. In the first three cohorts, ACTR707 was well-tolerated in combination with rituximab. No dose-limiting toxicities (DLTs), no adverse events of cytokine release syndrome (CRS), and no severe neurological adverse events including neurotoxicity have been reported in Cohorts 1, 2 and 3 as of the May 2019 cutoff. Serious adverse events that were assessed by the investigator as possibly related to ACTR707 include two cases of febrile neutropenia and one case of cytopenia in Cohorts 1 and 2 (Table 2).|
|Table 2: ACTR707 Preliminary Phase 1 trial safety results in r/r NHL (Cohorts 1-3)|
|Safety Event (1)||Cohort 1
|Severe neurologic events (> Grade 3)||0||0||0|
|CRS (any grade)||0||0||0|
|(1) Data cutoff as of May 2019|
- Cohort 4 (80M ACTR707+ T cells) enrollment proceeding in ATTCK-20-03: Enrollment in Cohort 4 of ATTCK-20-03 is complete and
Unumplans to report updated results from ATTCK-20-03, including data from patients in Cohort 4, in late 2019.
ACTR707 Solid Tumor Program Highlights:
Phase 1 trial (ATTCK-34-01) with ACTR707 in HER2+ advanced solid tumor cancers ongoing: Clinical trial site activation, patient identification, screening and enrollment continues in the first dose cohort of ATTCK-34-01, a Phase 1, multicenter, open-label, single-arm, dose-escalation trial evaluating ACTR T cells (ACTR707) in combination with trastuzumab for the treatment of patients with HER2+ advanced cancers.
Preclinical data demonstrate that, unlike traditional trastuzumab-based CAR-T cells that target HER2, ACTR707+ T cells administered with trastuzumab are highly selective for HER2-overexpressing tumor cells and discriminate against cells from normal tissues that express low levels of HER2. The preclinical activity of ACTR707+ T cell has been shown to be dose-dependent demonstrating control of ACTR707 activity by modulation of trastuzumab concentration. Together, the preclinical data suggest that ACTR cells in combination with trastuzumab may exhibit an improved clinical therapeutic index.
BOXR Solid Tumor Program Highlights:
- Preclinical development ongoing for BOXR1030 targeting GPC3+ advanced cancers: Unum’s Bolt-On Chimeric Receptor (BOXR) platform is designed to improve engineered T cell functionality by identifying and incorporating a “bolt-on” transgene to overcome resistance of the solid tumor microenvironment to T cell attack. BOXR bolt-on transgenes identified in this platform are designed to address a variety of immunosuppressive mechanisms of solid tumors including metabolic competition, immune suppressor cells, and exhaustion due to chronic stimulation. These transgenes could offer the potential to add new functionality to T cells not achievable by traditional small molecule or antibody-based approaches. In addition, the BOXR bolt-on transgenes may be incorporated into several different types of therapeutic T cells, including ACTR T cells and CAR-T cells. Using a variety of BOXR bolt-on transgenes and tumor targeting technologies,
Unumis building a pipeline of preclinical candidates to address a diverse range of solid tumor indications.
In early 2019,
Unumnominated BOXR1030 as the first product candidate from the BOXR platform. In addition to research to further characterize its mechanism of action, preclinical studies of BOXR1030 are underway to support the filing of an investigational new drug (IND) application for BOXR1030. Unumplans to present preclinical data regarding BOXR1030 in the second half of 2019.
ACTR087 Hematologic Program Highlights:
- Dose escalation continuing in Phase 1 (ATTCK-17-01) trial in multiple myeloma: Dose escalation continued during the second quarter in the ATTCK-17-01 trial combining ACTR087 with low doses of SEA-BCMA antibody. Enrollment and dosing of patients is complete in Cohort 4 (30M ACTR087+ T cells and 2.0 mg/kg SEA-BCMA) and Cohort 5 (50M ACTR087+ T cells and 2.0 mg/kg SEA-BCMA).
Unumexpects to report data from multiple dose cohorts in the second half of 2019.
- Treatment continuing for responding patients in Phase 1 (ATTCK-20-2) trial in non-Hodgkin lymphoma: In
July 2019, Unumannounced that the U.S. Food and Drug Administration( FDA) placed a clinical hold (since communicated by the FDAas a partial clinical hold) on the Phase 1 trial (ATTCK-20-2) evaluating Unum’s ACTR087 in combination with rituximab in patients with CD20+ r/r NHL. The clinical hold was initiated following the submission of a safety report by Unumto the FDAregarding one patient in the safety expansion cohort of the trial who experienced serious adverse events including neurotoxicity, cytomegalovirus infection, and respiratory distress. As an update to this case, this patient subsequently experienced septic shock that was fatal and reported by the investigator as related to ACTR087. Patients who previously received ACTR087 and have ongoing clinical responses continue to receive rituximab infusions, with continued monitoring for adverse events. Unumcontinues to work closely with the FDAto further review these events and plans to report data from the ATTCK-20-2 trial at the end of 2019.
- Announced new additions to its leadership team including
Matthew Osborneas Chief Financial Officer, Mert Aktaras of Head of Business and Corporate Development and Jessica Sachs, M.D., as Chief Medical Officer replacing Michael Vasconcelles, M.D., who transitioned to a clinical advisory role. Each new executive has a proven track record of excellence and adds decades of experience to the Unumleadership team.
- Announced the appointments of
Arlene Morrisand Matthew Rosto its Board of Directors. Ms. Morris and Mr. Ros replaced Robert Perezand Liam Ratcliffe, who transitioned from Unum’s Board of Directors in conjunction with their new positions within the biotechnology industry. Ms. Morris and Mr. Ross bring significant commercial, clinical and operational experience within the oncology field. Ms. Morris brings extensive corporate and business development experience in the pharmaceutical and biotechnology industries from numerous management and board roles, while Mr. Ros adds specific commercial experience, particularly with oncology products.
- Entered into an agreement with
Harbour Antibodies BV, a wholly-owned subsidiary of Harbour BioMed, granting Unumrights to utilize Harbour Antibodies’ H2L2 Harbour Mice® platform. The agreement enables Unumto discover and incorporate fully-human antibody sequences into its novel ACTR and BOXR platforms to further enable and accelerate Unum’s preclinical discovery and development efforts.
Second Quarter 2019 Financial Results
- Collaboration Revenue: Collaboration revenue recognized during the second quarter ended
June 30, 2019was $3.1 million, compared to $1.7 millionin the same period of 2018. The increase reflects the recognition of a portion of the upfront payment received from Seattle Genetics, Inc. under Unum’s collaboration agreement as well as reimbursements of research and development costs attributed to the collaboration agreement.
- R&D Expenses: Research and development expenses were
$10.6 million for the second quarter ended June 30, 2019, compared to $9.1 million for the same period of 2018. The increase primarily reflects higher clinical trial costs for the active Phase 1 trials, as well as increased personnel-related costs.
- G&A Expenses: General and administrative expenses for the second quarter ended
June 30, 2019, were $3.1 million, compared to $2.0 million for the same period of 2018. The increase is primarily related to higher personnel related costs due to increased headcount and increased expenses around operating as a public company.
- Net Loss: Net loss attributable to common stockholders was $10.5 million, or $0.34 per share, for the second quarter ended
June 30, 2019, and $9.0 million, or $0.31 per share, for the same period of 2018.
- Cash and Cash Equivalents: As of
June 30, 2019, Unumhad cash and cash equivalents of $55.9 million. Unumbelieves that its existing cash and cash equivalents will fund operating expenses and capital expenditure requirements into early 2021.
Investor Call and Webcast Information
Forward looking Statements
This press release contains forward-looking statements including, without limitation, statements regarding our future expectations, plans and prospects, including projections regarding future revenues and financial performance, our long-term growth, enrollment and results for our preclinical and clinical activities, the development of our product candidates, including the lead ACTR product candidates and the BOXR platform and product candidates, non-clinical or clinical options to resolve the partial clinical hold on ATTCK-20-2, and the anticipated timing and success of any of our preclinical studies, clinical trials and regulatory filings, as well as other statements containing the words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar expressions, constitute forward-looking statements within the meaning of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, as amended. We may not actually achieve the forecasts disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results could differ materially from the projections disclosed in the forward-looking statements we make as a result of a variety of risks and uncertainties, including risks related to the accuracy of our estimates regarding expenses, future revenues, capital requirements, and the need for additional financing, the success, cost and timing of our product development activities and clinical trials, our ability to obtain and maintain regulatory approval for our product candidates, and the other risks and uncertainties described in the "Risk Factors" sections of our public filings with the
Stern Investor Relations, Inc.
CONSOLIDATED STATEMENTS OF OPERATIONS
(unaudited, $ in thousands, except share and per share amounts)
|Three Months Ended June 30,||Six Months Ended June 30,|
|Research and development||10,617||9,126||23,020||17,268|
|General and administrative||3,062||1,979||5,553||3,043|
|Total operating expenses||13,679||11,105||28,573||20,311|
|Loss from operations||(10,541||)||(9,439||)||(22,382||)||(16,425||)|
|Other income (expense):|
|Other income, net||—||157||—||327|
|Total other income, net||25||416||175||667|
|Accretion of redeemable convertible preferred stock to redemption value||—||—||—||(16||)|
|Net loss attributable to common stockholders||$||(10,516||)||$||(9,023||)||$||(22,207||)||$||(15,774||)|
|Net loss per share attributable to common stockholders, basic and diluted||$||(0.34||)||$||(0.31||)||$||(0.73||)||$||(0.80||)|
|Weighted average common shares outstanding, basic and diluted||30,505,773||29,155,790||30,295,557||19,732,542|
CONSOLIDATED SELECTED BALANCE SHEET DATA
(unaudited, in thousands)
|June 30, 2019||December 31, 2018|
|Cash, cash equivalents and marketable securities||$||55,863||$||78,594|
|Total stockholders' equity||$||39,758||$||60,234|
Source: Unum Therapeutics Inc.