On May 10, 2021 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported financial results for the first quarter ended March 31, 2021 and provided a business update (Press release, Mersana Therapeutics, MAY 10, 2021, View Source [SID1234579571]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The recent initiation of UPLIFT, a single-arm registrational strategy evaluating UpRi in platinum-resistant ovarian cancer, speaks to the team’s commitment to achieving key milestones and dedication to developing therapies for people living with cancer. We believe UpRi has demonstrated promising activity and a differentiated tolerability profile in studies to date in patients with heavily-pretreated ovarian cancer and limited options. UPLIFT has been designed to increase the potential for label differentiation, speed to market, and the probability of success. We also remain on track to initiate the UPGRADE umbrella combination study in the third quarter of 2021 as a first step in bringing UpRi to patients in earlier lines of therapy and establishing UpRi as a foundational medicine in ovarian cancer," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "We are excited to continue this productive year by building out our maturing pipeline of innovative ADC candidates with the potential to address unmet medical needs across multiple different tumor types."
Recent Highlights and Anticipated Milestones
Upifitamab Rilsodotin (UpRi, previously XMT-1536), first-in-class Dolaflexin ADC targeting NaPi2b:
Initiated UPLIFT, a single-arm registration strategy in platinum-resistant ovarian cancer. In April 2021, the Company announced the initiation of patient dosing in UPLIFT, a single-arm registration strategy evaluating the safety and efficacy of UpRi in patients with platinum-resistant ovarian cancer who have received up to four lines of therapy. Consistent with the bevacizumab label, patients previously treated with three or four lines of therapy may enroll without regard to prior bevacizumab treatment. There is no exclusion for patients with baseline peripheral neuropathy. Patients may enroll without regard to NaPi2b expression; however, the role of the biomarker will be evaluated. The primary endpoint will be the objective response rate (ORR) in the high NaPi2b population and the secondary endpoints will be the ORR regardless of NaPi2b expression, as well as duration of response and safety. UPLIFT is an amendment to the ongoing multinational, multi-center, open label study protocol, and the Company expects to enroll approximately 100 patients with high NaPi2b expression and up to 180 patients overall.
In April 2021, the Company announced its plans to use Tumor Proportion Score (TPS) greater than or equal to 75% as the predefined threshold for high NaPi2b expression in UPLIFT. In the ovarian cancer expansion study data presented to date, TPS ≥ 75% resulted in an objective response rate (ORR) of 39% in high NaPi2b patients relative to an ORR of 28% in the overall population. As part of its diagnostic development plan, the Company evaluated TPS methodology in the expansion portion of the Phase 1 study in ovarian cancer and demonstrated that TPS captures a broad dynamic range of expression values, enriches for response, and offers reproducibility advantages across commercial labs. The Company also disclosed the steps it has taken to develop a robust, predictive and reproducible commercial diagnostic assay which will be used in a prospectively defined retrospective analysis in UPLIFT.
UPGRADE combination dose escalation umbrella study in ovarian cancer expected to initiate in the third quarter of 2021. The Company plans to initiate the UPGRADE study in the third quarter of 2021 to evaluate the combination of UpRi with other agents, starting with a platinum combination. The Phase 1, open-label, dose-escalation portion of the study will determine the maximum tolerated dose (MTD) and safety and tolerability of a once-every-four-week (Q4W) administration of UpRi in combination with Q4W administration of carboplatin for six cycles followed by UpRi monotherapy in platinum-sensitive patients with high-grade serous ovarian cancer who have received 1-2 prior platinum-based regimens. Patients will not be preselected for NaPi2b expression; however, archival or fresh tissue will be required for retrospective assessment of expression. Upon completion of the dose-escalation portion of the study, the Company plans to initiate the expansion portion in combination with carboplatin for six cycles followed by UpRi monotherapy to assess feasibility as well as efficacy to inform next steps in this broader and less heavily-pretreated patient population.
NSCLC adenocarcinoma cohort of the expansion portion of Phase 1 study continues to enroll patients. The Company is on track to recruit approximately 40 patients in the expansion phase of the study. The Company plans to report interim data in the second half of 2021.
XMT-1592, first Dolasynthen ADC targeting NaPi2b:
Phase 1 dose escalation study of XMT-1592 is ongoing, with interim data anticipated in the second half of 2021. The Company has exceeded the maximum tolerated dose and continues to further explore dose and schedule. The Company plans to disclose interim data in the second half of 2021 and further outline the XMT-1592 development plan in NSCLC in the fourth quarter of 2021.
XMT-1660, first-in-class Dolasynthen ADC targeting B7-H4:
Investigational New Drug (IND)-enabling studies of XMT-1660 ongoing with Phase 1 studies expected to start in early 2022. B7-H4 is expressed in high unmet need tumors such as breast, endometrial and ovarian. B7-H4 is expressed on both tumor cells and immunosuppressive tumor-associated macrophages (TAMs). This provides the potential for both a direct, cytotoxic antitumor effect as well as for additional payload delivery to the tumor microenvironment that can further contribute to immunogenic cell death, dendritic cell activation, and stimulation of an immune response consistent with the features of the Company’s unique DolaLock payload. In a poster presented at the Virtual 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April, the Company presented preclinical data demonstrating XMT-1660’s superior efficacy compared to other potential candidate B7-H4 ADCs, covering a range of drug-to-antibody ratios, in multiple triple-negative breast cancer models as well as a ER+/HER2- breast cancer model. These data further support the clinical development of XMT-1660 for the treatment of B7-H4-expressing tumors.
XMT-2056, first Immunosynthen STING-agonist ADC:
IND-enabling studies of XMT-2056 ongoing with Phase 1 studies expected to start in early 2022. In April 2021, the Company presented two posters at AACR (Free AACR Whitepaper) highlighting preclinical efficacy of XMT-2056 as well as mechanistic data representative of the Immunosynthen platform. These data demonstrated the differentiation of XMT-2056 and its ability to induce robust anti-tumor immune activity, with only minimal increases in systemic cytokine levels, and a significant benefit over the benchmark IV-administered free STING-agonist in mice. Preclinical mechanistic data suggests that the tumor cell-intrinsic STING pathway can be activated in the presence of cues from immune cells, a potential key differentiator from other innate immune activation approaches. Further, in vitro studies showed that blocking Type III interferons (IFNs) inhibits the production of key cytokines and cancer cell killing induced by STING-agonist ADC treatment, pointing to a potentially important role for Type III IFNs in anti-tumor immune responses downstream of STING pathway activation in tumor cells. The Company plans to disclose the target for the XMT-2056 in the fourth quarter of 2021.
Corporate
Appointed Alejandra Carvajal as Senior Vice President and Chief Legal Officer. Ms. Carvajal was most recently the Chief Legal Officer, General Counsel & Secretary at Momenta Pharmaceuticals, where she led the company’s legal operations through both business restructuring and successful execution of an acquisition by Johnson & Johnson for $6.5 billion. She also served as a key strategic legal partner in the company’s financing, business development, and contractual decision-making efforts. Prior to joining Momenta, Ms. Carvajal served as the Vice President, General Counsel at Cerulean Pharma. Previously, she worked at Millennium Pharmaceuticals in several positions of increasing seniority.
Appointed Allene Diaz to Board of Directors. Ms. Diaz has over thirty years of experience in the pharmaceutical industry most recently serving as Senior Vice President of R&D portfolio management and decision sciences at GlaxoSmithKline. She previously held senior strategic product planning and commercial roles at Tesaro and Merck KGaA. She has contributed to the development, launch and commercialization of multiple global cancer therapies. Ms. Diaz is currently on the board of both BCLS Acquisition Corporation and Allena Pharmaceuticals, having previously served as a non-executive director at Erytech for three years before her current board positions.
Upcoming Events
Mersana will participate in a virtual presentation at the Jefferies Healthcare Conference scheduled for June 1-4, 2021.
A Trial in Progress poster detailing the design of the UPLIFT single-arm registration strategy evaluating UpRi in platinum resistant ovarian cancer will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Annual Meeting scheduled for June 4-8, 2021.
First Quarter 2021 Financial Results
Cash and cash equivalents as of March 31, 2021, were $228.4 million, compared to $255.1 million in cash and cash equivalents as of December 31, 2020. In addition, the Company has the option to draw additional funds through its debt financing agreement with Silicon Valley Bank.
Net cash used in operating activities in the first quarter of 2021 was $27.0 million. The Company expects that its available funds will be sufficient to support its operating plan commitments for approximately two years.
Research and development expenses for the first quarter of 2021 were approximately $27.4 million, compared to $12.2 million for the same period in 2020. The difference was primarily due to an increase in UpRi and XMT-1592 manufacturing, clinical and regulatory expenses, an increase in manufacturing activities for preclinical and discovery stage programs and an increase in headcount. Non-cash stock-based compensation expense included in research and development expenses increased by $1.5 million, primarily related to an increase in the valuation of stock-based awards as a result of stock appreciation.
General and administrative expenses for the first quarter of 2021 were approximately $7.2 million, compared to $4.9 million during the same period in 2020 primarily due to an increase in headcount and consulting and professional fees. Non-cash stock-based compensation expense included in general and administrative expenses increased by $0.9 million, primarily related to an increase in the valuation of stock-based awards as a result of stock appreciation.
Net loss for the first quarter of 2021 was $34.7 million, or $0.50 per share, compared to net loss of $16.9 million, or $0.35 per share, for the same period in 2020. Weighted average common shares outstanding for the quarters ended March 31, 2021 and March 31, 2020 were 68,987,857 and 47,988,630, respectively.
Conference Call Details
Mersana Therapeutics will host a conference call and webcast today at 4:30 p.m. ET to report financial results for the first quarter 2021 and provide certain business updates. To access the call, please dial 877-303-9226 (domestic) or 409-981-0870 (international) and provide the Conference ID 5046849. A live webcast of the presentation will be available on the Investors & Media section of the Mersana website at www.mersana.com.