Mersana Reports Updated Data from the XMT-1536 Phase I Dose Escalation Study; Raises U.S. $ 65 Million

Mersana Therapeutics, 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 needs, has raised gross proceeds of approximately U.S. $ 65 million through its At-the-Market (ATM) facility.

Participants included Avoro Capital Advisors, Bain Capital Life Sciences, Consonance Capital Investors and David Mott, Mersana’s Chairman of the Board. The Company sold approximately 8.9 million shares of the Company’s common stock at a purchase price of U.S. $ 5.59 and 2.0 million shares at the closing price of U.S. $ 7.74, in each case the market price at the time of sale. Cowen is acting as the sales agent for the ATM facility.

The additional funds raised through the ATM strengthen Mersana’s balance sheet and will be used to advance its pipeline, including the clinical development of XMT-1536 and XMT-1592, as well as for working capital and other general corporate purposes.

Updated study data
In late March 2020, Mersana released updated efficacy and safety data in patients with ovarian cancer and non-small cell lung cancer (NSCLC) adenocarcinoma from its ongoing Phase I dose-escalation study evaluating XMT-1536.[1][2]

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XMT-1536, Mersana’s first-in-class ADC targeting the sodium-dependent phosphate transport protein NaPi2b (SLC34A2), utilizes the company’s proprietary Dolaflexin platform technology designed to deliver an average of 10-12 DolaLock (auristatin) payload molecules per antibody.

NaPi2b is broadly expressed in non-small cell lung cancer adenocarcinoma and ovarian cancer.

ASCO 2019 and follow-up
Interim data from the ongoing XMT-1536 Phase I dose-escalation study presented at ASCO in June 2019 showed encouraging clinical activity with confirmed responses and prolonged stable disease in heavily pretreated patients, without pre-selection for NaPi2b expression. The initial data showed that XMT-1536 was well-tolerated without the severe toxicities commonly seen with other ADCs such as neutropenia, ocular toxicities, or peripheral neuropathy.[3]

However, the experts considered the data for XMT-1536 presented in March 2020 disappointing, with tumor shrinkage reported in just five heavily pretreated patients, and only three with tumors smaller than when they began taking the investigational drug, none of the patients achieving complete remission.

However, researchers at Mersana concluded that the results of the ascending-dose phase study were still encouraging enough to continue treating patients with lung and ovarian cancer, dosing them at the highest tolerable dosage in an extension study.

“[The] data demonstrate that XMT-1536, our first-in-class Dolaflexin ADC targeting NaPi2b, delivers confirmed responses and durable stable disease in heavily pretreated ovarian cancer and NSCLC adenocarcinoma patients who have exhausted all other treatment options,” noted Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics.

“These data also show that XMT-1536 is well tolerated without the severe toxicities of other ADC platforms such as neutropenia, neuropathy and ocular toxicity. Moreover, these data establish the potential for a biomarker-response relationship to identify patients most likely to benefit from XMT-1536,” she added.

“We look forward to advancing XMT-1536 for both ovarian cancer and NSCLC adenocarcinoma patients. Having already accumulated meaningful patient experience in the expansion cohorts, we remain on track to provide an interim update in the second quarter of 2020,” Protopapas concluded.

Study results
Of the 59 patients enrolled, tumor types included 37 ovarian cancer, 11 NSCLC adenocarcinoma, and 11 other tumor types previously disclosed at lower dose levels. Patients were heavily pre-treated, with a median of five prior lines of treatment (range 1-10). These data include new patients dosed at 30, 36 and 43 mg/m².

The majority of ovarian cancer patients had received prior bevacizumab or PARP inhibitors. All NSCLC adenocarcinoma patients had received prior platinum and immunotherapy.

Safety profile consistent with previously reported data at lower doses. 

• The most common treatment-related adverse events (TRAEs) were Grade 1-2 nausea, fatigue, headache and the most frequent Grade 3 TRAE was transient AST elevation.
• There were no dose-limiting toxicities observed in the 43 mg/m² cohort.
• There was no reported severe neutropenia, peripheral neuropathy or ocular toxicity.

Additional confirmed responses in heavily pretreated patients and the favorable biomarker-response trends observed.

• First confirmed partial response seen in an NSCLC adenocarcinoma patient with prior treatments including carboplatin, pemetrexed, paclitaxel, and nivolumab.
• At the 43 mg/m² dose level, 2/7 (29%) patients achieved partial responses (PRs) and 4/7 (57%) patients achieved stable disease (SD) for a disease control rate (DCR) of 6/7 (86%). In January 2020, the expansion portion of the Phase I study dose was amended from 36 mg/m² to 43 mg/m² for newly enrolled patients.
• For the subset of evaluable patients treated at >30 mg/m² who had higher NaPi2b expression, 5/15 (33%) achieved PR and 6/15 (40%) achieved SD for a DCR of 11/15 (73%).
• In contrast, for the subset of evaluable patients treated at >30 mg/m² who had lower NaPi2b expression, 0/9 (0%) achieved PR and 5/9 (55%) achieved SD for a DCR of 5/9 (55%).

*Excludes 3 patients discontinued due to investigator/patient choice and 1 without RECIST scan
**Hypocellular specimen/indeterminate for H-score or not determined yet
^O Higher NaPi2b Expression: at / above lowest H-score at which response observed (>110)
^OO Lower NaPi2b Expression: below the lowest H-score at which response observed (<110)

Mersana plans to enroll approximately 45 patients in each of ovarian cancer and NSCLC adenocarcinoma patient cohorts in the expansion portion of the XMT-1536 Phase I study. Interim results from the dose-expansion study are expected to be released in the second quarter of 2020.

Later this year Mersana is also expected to begin a proof-of-concept study with XMT-1592, another investigational agent targeting NaPl2b.

Clinical trial
First-in-Human Study of XMT-1536 in Cancers Likely to Express NaPi2b – NCT03319628

Reference
[1] Lee EK, Liu JF. Antibody-drug conjugates in gynecologic malignancies. Gynecol Oncol. 2019;153(3):694–702. doi:10.1016/j.ygyno.2019.03.24
[2] Garcia, D. Mersana Therapeutics Initiates Expansion Study of XMT-1536 in Platinum-Resistant Ovarian Cancer and Non-Small Cell Lung Cancer. ADC Review | J. Antibody-drug Conjugates. Online. August 20, 2020.
[3] Tolcher AW, Ulahannan SV, Papadopoulos KP, Edenfield WJ, Matulonis UA, Burns TF, Mosher R, Huebner D, Hailman E, Burris III HA, Moore KN, Hamilton EP. Phase 1 dose-escalation study of XMT-1536, a novel NaPi2b-targeting antibody-drug conjugate (ADC), in patients (pts) with solid tumors likely to express NaPi2b. ASCO 2019 Abstract #255157