Sesen Bio Reports Positive, Preliminary Data Update from Phase 3 VISTA Trial for High-Risk Non-Muscle Invasive Bladder Cancer
Updated 12-month Phase 3 Data will Serve as the Basis for Submission of the BLA
On Track for Anticipated Initiation of BLA Submission in 4Q 2019
“After two very positive meetings with the
Phase 3 VISTA Trial Progress
- Updated Primary and Secondary Endpoint Data from Phase 3 VISTA Trial Support a Growing Body of Evidence Demonstrating the Clinically Meaningful Anti-tumor Activity of Vicinium: In May,
Sesen Bio announced updated preliminary data from its ongoing Phase 3 VISTA trial, a single-arm, 24-month, multi-center clinical trial designed to support the approval of Vicinium for the treatment of patients with high-risk, BCG-unresponsive NMIBC.The trial completed registration in the second quarter of 2018, with a total of 133 patients across three cohorts based on histology and time to disease recurrence after adequate BCG treatment (at least two courses of BCG with at least five doses in the first course and two doses in the second course). Primary efficacy endpoints consist of complete response rate and duration of response for patients in Cohort 1. Secondary efficacy endpoints include time to disease recurrence for patients in Cohort 3, and time to cystectomy, progression-free survival, event-free survival, and overall survival for patients across all cohorts. As of theMay 29, 2019 data cut, updated preliminary primary and secondary efficacy data for each of the trial cohorts were as follows:
Cohort 1 Complete Response Rate, Evaluable Population |
||||
Time point |
Evaluable Patients* |
Complete Response Rate |
||
3-months |
n=82 |
39% |
||
6-months |
n=82 |
26% |
||
9-months |
n=82 |
20% |
||
12-months |
n=82 |
17% |
Patients with Carcinoma in situ with or without papillary disease that was determined to be refractory or recurred within six months of their last course of adequate BCG.
*Response-evaluable population includes any modified intention to treat (mITT) subject who completed the induction phase.
Cohort 2 Complete Response Rate, Evaluable Population |
||||
Time point |
Evaluable Patients* |
Complete Response Rate |
||
3-months |
n=7 |
57% |
||
6-months |
n=7 |
57% |
||
9-months |
n=7 |
43% |
||
12-months |
n=7 |
14% |
Patients with Carcinoma in situ with or without papillary disease that was determined to be refractory or recurred after six months, but less than or equal to 11 months, after their last course of adequate BCG.
*Response-evaluable population includes any mITT subject who completed the induction phase.
Pooled Cohorts 1 and 2 Complete Response Rate, Evaluable Population |
||||
Time point |
Evaluable Patients* |
Complete Response Rate
|
||
3-months |
n=89 |
40% (30%- 51%) |
||
6-months |
n=89 |
28% (19%-39%) |
||
9-months |
n=89 |
21% (13%-31%) |
||
12-months |
n=89 |
17% (10%-26%) |
Patients with Carcinoma in situ with or without papillary disease that was determined to be refractory or recurred less than 11 months after their last course of adequate BCG.
*Response-evaluable population includes any mITT subject who completed the induction phase.
- Duration of Response: The median duration of response for patients in Cohort 1 (n=86) is 273 days (95% CI, 122-NA), using the Kaplan-Meier method. Additional ad hoc analysis of pooled data for all patients with Carcinoma in situ (Cohorts 1 and 2, n=93) shows that among patients who achieved a complete response at 3 months, 52% had a complete response for a total of 12 months or longer after starting therapy, using the Kaplan-Meier method.
- Time to Disease Recurrence: High-risk papillary (Ta or T1) NMIBC is associated with higher rates of progression and recurrence. Therefore, time to disease recurrence is a key secondary endpoint for patients with high-risk papillary-only NMIBC. The median time to disease recurrence for patients in Cohort 3 (n=40) is 402 days (95% CI, 170-NA), using the Kaplan-Meier method.
- Time to Cystectomy: The
FDA guidance states that the goal of therapy in patients with BCG-unresponsive NMIBC is to avoid cystectomy. Therefore, time to cystectomy is a key secondary endpoint in the VISTA trial. Across all 133 patients treated with Vicinium, >75% of patients are estimated to remain cystectomy-free at 2.5 years, using the Kaplan-Meier method. Additional ad hoc analysis of responders and non-responders for all patients shows that approximately 88% of responders are estimated to remain cystectomy-free at 3 years. - Progression-Free Survival: 90% of all 133 patients treated with Vicinium are estimated to remain progression-free for 2 years or greater, using the Kaplan-Meier method. Progression-free is defined as the time from the date of first dose of study treatment to disease progression (e.g. T2 or more advanced disease) or death as a first event.
- Event-Free Survival: 29% of all 133 patients treated with Vicinium are estimated to remain event-free at 12 months, using the Kaplan-Meier method. Event-free survival is defined as the time from the date of first dose of study treatment to disease recurrence, progression, or death as a first event.
- Overall Survival: 96% of all 133 patients treated with Vicinium are estimated to have an overall survival of 2 years or greater, using the Kaplan-Meier method. Overall survival is defined as the time from the date of first dose of study treatment to death from any cause.
- Vicinium Continues to be Well-tolerated by Patients in the Phase 3 VISTA Trial: As of the
May 29, 2019 data cut, in patients across all cohorts (n=133), 95% of adverse events were Grade 1 or 2. The most commonly reported treatment-related adverse events were dysuria (14%), hematuria (13%) and urinary tract infection (12%) – all of which are consistent with the profile of bladder cancer patients and the use of catheterization for treatment administration. These adverse events were determined by the clinical investigators to be manageable and reversible, and only four patients (3%) discontinued treatment due to an adverse event. Serious adverse events (SAEs), regardless of treatment attribution, were reported in 14% of patients. There were four treatment-related SAEs reported in three patients including acute kidney injury (Grade 3), pyrexia (Grade 2), cholestatic hepatitis (Grade 4) and renal failure (Grade 5). There were no age-related increases in adverse events observed in the Phase 3 VISTA trial.
Vicinium Regulatory Pathway Updates
- Bulk Drug Substance from the Full-Scale GMP Manufacturing Run at
FUJIFILM Met all Phase 3 Quality Release Specifications: InApril 2019 , the first full, commercial-scale GMP run was completed atFUJIFILM Diosynth Biotechnologies U.S.A., Inc (FUJIFILM ). Release testing of the bulk drug substance has been completed and all Phase 3 release specifications were met, further de-risking the Company’s manufacturing technology transfer toFUJIFILM and the Company’s Analytical Comparability Plan. - Recent positive interactions with the
FDA reaffirm the Company’s confidence in the regulatory and commercial pathway for Vicinium- Type C CMC Meeting held on
May 20, 2019 . In conjunction with the technology transfer of Vicinium production toFUJIFILM , the Company has reached agreement with theFDA on the Analytical Comparability Plan, and that, subject to final comparability data to be provided in the BLA submission, no additional clinical trials to establish comparability are deemed necessary at this time. -
Pre-BLA Meeting held on
June 6, 2019 . The Company has reached alignment with theFDA on the regulatory approval pathway for Vicinium:-
The clinical, nonclinical and clinical pharmacology data, as well as the safety database, are sufficient to support a BLA submission, and no additional clinical trials are necessary for a BLA submission.
FDA recommended submission under an Accelerated Approval Pathway and Rolling Review.-
Per the official
FDA minutes received post-meeting, theFDA stated that the pre-approval inspection (PAI) may be completed at the time of PPQ manufacturing, which the Company believes will further de-risk the CMC review timeline. Expected Advisory Committee (ODAC) meeting post-BLA submission to review the benefit-risk profile of Vicinium, given there have been no product approvals in this indication in the past twenty years.
-
- Type C CMC Meeting held on
Key Upcoming Corporate Milestones:
- Type B CMC meeting to align on the submission strategy of CMC Module 3.
- Type C meeting to discuss the details of a post-marketing confirmatory trial in support of the Accelerated Approval Pathway for Vicinium.
- Initiation of BLA submission including nonclinical and clinical modules 1, 2, 4 and 5.
Second Quarter 2019 Financial Results
- Cash Position: Cash and cash equivalents were
$64.9 million as ofJune 30, 2019 , compared to$50.4 million as ofDecember 31, 2018 . - Revenue: No revenue was recorded for the three months ended
June 30, 2019 , nor for the comparable period in 2018. - R&D Expenses: Research and development (R&D) expenses for the second quarter of 2019 were
$7.9 million compared to$2.8 million in R&D expenses for the same period in 2018. The increase of$5.1 million was due primarily to costs related to the ongoing manufacturing process and technology transfer withFUJIFILM and increased internal and external staffing costs, partially offset by reduced expenses related to the Phase 3 VISTA trial. - G&A Expenses: General and administrative expenses for the second quarter of 2019 were
$2.6 million compared to$2.4 million for the same period in 2018. The increase was due primarily to higher professional fees and internal staffing costs. - Net Loss: Net loss was
$54.3 million , or$0.67 per share, for the second quarter of 2019, compared to$9.0 million , or$0.16 per share, for the second quarter of 2018. Included in the 2019 net loss is a charge for$44.0 million to increase the Company’s contingent consideration liability for higher estimated commercial sales volumes of Vicinium.
About the VISTA Clinical Trial
The VISTA trial is an open-label, multicenter, single-arm Phase 3 clinical trial evaluating the efficacy and tolerability of Vicinium® as a monotherapy in patients with high-risk, bacillus Calmette-Guérin, or BCG, unresponsive non-muscle invasive bladder cancer (NMIBC). The primary endpoints of the trial are the complete response rate and the duration of response in patients with Carcinoma in situ with or without papillary disease. Patients in the trial receive locally administered Vicinium twice a week for six weeks, followed by once-weekly treatment for another six weeks, then treatment every other week for up to two years. To learn more about the Phase 3 VISTA trial, please visit www.clinicaltrials.gov and search the identifier NCT02449239.
About Vicinium®
Vicinium, a locally-administered fusion protein, is Sesen Bio’s lead product candidate being developed for the treatment of high-risk non-muscle invasive bladder cancer (NMIBC). Vicinium is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A. Vicinium is constructed with a stable, genetically engineered peptide tether to ensure the payload remains attached until it is internalized by the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical trials conducted by
About
Cautionary Note on Forward-Looking Statements
Any statements in this press release about future expectations, plans and prospects for the Company, the Company’s strategy, future operations, and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and conduct of clinical trials, the possibility that the preliminary data of the Phase 3 VISTA trial are not indicative of final clinical results and final clinical trial results may not be positive with regard to the safety or efficacy of Vicinium, our ability to successfully develop our product candidates and complete our planned clinical programs, expectations regarding future meetings with the
SESEN BIO, INC. | ||||||||||||||
CONDENSED CONSOLIDATED BALANCE SHEETS | ||||||||||||||
(in thousands) | ||||||||||||||
(unaudited) | ||||||||||||||
June 30, | December 31, | |||||||||||||
2019 |
2018 |
|||||||||||||
Assets | ||||||||||||||
Current assets: | ||||||||||||||
Cash and cash equivalents |
$ |
64,931 |
|
$ |
50,422 |
|
||||||||
Prepaid expenses and other current assets |
|
2,598 |
|
|
1,334 |
|
||||||||
Total current assets |
|
67,529 |
|
|
51,756 |
|
||||||||
Property and equipment, net |
|
376 |
|
|
321 |
|
||||||||
Restricted cash |
|
20 |
|
|
20 |
|
||||||||
Intangible assets |
|
46,400 |
|
|
46,400 |
|
||||||||
Goodwill |
|
13,064 |
|
|
13,064 |
|
||||||||
Other assets |
|
223 |
|
|
- |
|
||||||||
Total assets |
$ |
127,612 |
|
$ |
111,561 |
|
||||||||
Liabilities and stockholders' equity | ||||||||||||||
Current liabilities: | ||||||||||||||
Accounts payable |
$ |
2,176 |
|
$ |
1,367 |
|
||||||||
Accrued expenses |
$ |
5,630 |
|
$ |
4,746 |
|
||||||||
Other current liabilities |
|
142 |
|
|
- |
|
||||||||
Total current liabilities |
|
7,948 |
|
|
6,113 |
|
||||||||
Other liabilities |
|
367 |
|
|
313 |
|
||||||||
Deferred tax liability |
|
12,528 |
|
|
12,528 |
|
||||||||
Contingent consideration |
|
91,400 |
|
|
48,400 |
|
||||||||
Stockholders' equity: | ||||||||||||||
Common stock |
|
101 |
|
|
77 |
|
||||||||
Additional paid-in capital |
|
262,107 |
|
|
230,154 |
|
||||||||
Accumulated deficit |
|
(246,839 |
) |
|
(186,024 |
) |
||||||||
Total stockholders' equity |
|
15,369 |
|
|
44,207 |
|
||||||||
Total liabilities and stockholders' equity |
$ |
127,612 |
|
$ |
111,561 |
|
SESEN BIO, INC. | ||||||||||||||||||||||
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS | ||||||||||||||||||||||
(unaudited) | ||||||||||||||||||||||
(in thousands, except per share data) | ||||||||||||||||||||||
Three Months Ended June 30, | Six Months Ended June 30, | |||||||||||||||||||||
2019 |
2018 |
2019 |
2018 |
|||||||||||||||||||
Operating expenses: | ||||||||||||||||||||||
Research and development |
|
7,944 |
|
|
2,779 |
|
|
12,630 |
|
|
6,034 |
|
||||||||||
General and administrative |
|
2,617 |
|
|
2,351 |
|
|
5,672 |
|
|
4,303 |
|
||||||||||
Loss from change in fair value of contingent consideration |
|
44,000 |
|
|
3,900 |
|
|
43,000 |
|
|
2,700 |
|
||||||||||
Total operating expenses |
|
54,561 |
|
|
9,030 |
|
|
61,302 |
|
|
13,037 |
|
||||||||||
Loss from operations |
|
(54,561 |
) |
|
(9,030 |
) |
|
(61,302 |
) |
|
(13,037 |
) |
||||||||||
Other income, net |
|
226 |
|
|
72 |
|
|
487 |
|
|
116 |
|
||||||||||
Net loss and comprehensive loss |
$ |
(54,335 |
) |
$ |
(8,958 |
) |
$ |
(60,815 |
) |
$ |
(12,921 |
) |
||||||||||
Net loss per share —basic and diluted |
$ |
(0.67 |
) |
$ |
(0.16 |
) |
$ |
(0.77 |
) |
$ |
(0.28 |
) |
||||||||||
Weighted-average number of common shares used in net | ||||||||||||||||||||||
loss per share —basic and diluted |
|
80,739 |
|
|
56,421 |
|
|
79,107 |
|
|
46,105 |
|
View source version on businesswire.com: https://www.businesswire.com/news/home/20190808005803/en/
Source:
Erin Clark, Vice President, Corporate Strategy and Investor Relations
ir@sesenbio.com