On January 3, 2019 Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage drug discovery and development company applying synthetic biology to beneficial microbes to develop novel living medicines, reported an overview of recent progress and outlined key objectives and anticipated milestones for 2019 (Press release, Synlogic, JAN 3, 2019, View Source [SID1234532396]).

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"2018 was a significant year for Synlogic as we advanced our two lead clinical programs and platform. We have demonstrated proof of mechanism in both programs in healthy volunteers and are currently evaluating safety and activity in patients with disease. In addition, we broadened our pipeline with the addition of our first immuno-oncology development candidate, SYNB1891," said Aoife Brennan, M.B. Ch.B., Synlogic’s president and chief executive officer. "In 2019 we look forward to presenting data from our two ongoing clinical programs that will inform the development of our Synthetic Biotic platform. With the recent expansion of our internal GMP-manufacturing capabilities, we are well positioned to maintain the momentum of the past year and continue to advance programs through clinical development as expeditiously as possible."

2019 Goals and Catalysts

Pipeline

SYNB1020: An orally delivered, first-in-class, Synthetic Biotic medicine designed for treatment of elevated blood ammonia levels (hyperammonemia) in chronic liver disease or genetic urea cycle disorders (UCDs).
In mid-2019, Synlogic expects to present top-line data from its randomized, double-blind, placebo -controlled Phase 1b/2a clinical trial evaluating SYNB1020 in patients with cirrhosis and elevated ammonia. The main endpoints of the study are safety and tolerability, as well as evidence of ammonia lowering in patients.
SYNB1618: An orally delivered, Synthetic Biotic medicine designed for the treatment of phenylketonuria (PKU).
In mid-2019, Synlogic expects to present top-line data from its randomized, double-blind, placebo-controlled Phase 1/2a clinical trial evaluating SYNB1618 in patients with PKU. The study is designed to evaluate safety and tolerability in this population as well as pharmacokinetics and pharmacodynamics as determined by the production of biomarkers specifically associated with SYNB1618 activity.
SYNB1891: Synlogic’s first immuno-oncology (IO) development candidate, a STING agonist-producing Synthetic Biotic medicine, designed to act as a dual innate immune activator, for the treatment of non-immunologically responsive solid tumors.
In the second half of 2019 the Company expects to file an IND application to enable advancement of SYNB1891 into a Phase 1 clinical study.
Pre-clinical data and early pipeline programs:
The company expects to publish and present data at major scientific and medical meetings throughout the year demonstrating the breadth and potential of its Synthetic Biotic platform.
Synlogic and AbbVie will continue to advance their ongoing collaboration to develop a Synthetic Biotic medicine for the treatment of inflammatory bowel disease (IBD).
Corporate

Synlogic ended the third quarter of 2018 with $133 million in cash and cash equivalents and expects that this will fund Company operations through 2020 under its current plan.
The Company will continue to explore additional strategic opportunities to expand the reach of its Synthetic Biotic platform.
2018 Accomplishments and Highlights:

Pipeline

SYNB1020:
Dosed first patient in Phase 1b/2a trial of SYNB1020 for the treatment of hyperammonemia in patients with cirrhosis and elevated ammonia. The clinical trial is a single and multiple dose-escalation, randomized, double-blind, placebo-controlled study of orally administered SYNB1020 in patients with cirrhosis and elevated blood ammonia, designed to evaluate safety, tolerability, kinetics, and pharmacodynamics as well as the ability of SYNB1020 to lower blood ammonia. Synlogic enrolled and treated an initial open-label sentinel cohort of six subjects with mild disease to ensure that SYNB1020 was safe in patients with liver disease who often have compromised barrier function and might be susceptible to infection. This part of the study is complete and Synlogic is enrolling patients with more advanced disease with elevated blood ammonia at baseline.
Presented data supporting continued development of SYNB1020 for the treatment of liver disease at the annual meeting of the American Association for the Study of Liver Diseases (AASLD). Synlogic presented data from a cross-sectional study designed to establish ammonia measurement parameters and ammonia levels in healthy volunteers at clinical sites that are participating in Synlogic’s ongoing Phase 1b/2a clinical trial of SYNB1020 in patients with cirrhosis and elevated ammonia. Preclinical data from a rat model were also presented by Synlogic’s collaborators that demonstrated dose-dependent lowering of blood ammonia by Synthetic Biotic strains designed to consume ammonia, confirming earlier preclinical observations in mouse models of liver disease.
SYNB1618:
Announced positive interim data from the healthy volunteer arm of its ongoing Phase 1/2a clinical trial evaluating SYNB1618 for the treatment of PKU. The data demonstrated a statistically significant, dose-dependent effect on treatment-associated biomarkers, indicating proof-of-mechanism, and also established a go-forward dose for the treatment arm in patients with PKU.
Published preclinical data in Nature Biotechnology identifying key biomarkers of SYNB1618 activity in healthy animal and disease models. The data demonstrated that oral administration of SYNB1618 significantly reduced blood phenylalanine (Phe) levels, the key metabolite associated with PKU, in mouse models of PKU and resulted in dose-dependent pharmacodynamics in healthy non-human primates (NHPs).
Fast Track designation granted to SYNB1618 for PKU by the U.S. Food and Drug Administration (FDA).
SYNB1891:
Presented preclinical data highlighting the potential of Synthetic Biotic medicines in IO and announced first IO clinical candidate at the annual meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). A webcast of the presentation is available on the Synlogic website. Data presented at the meeting demonstrate the platform’s potential for the treatment of cancer and inflammation and specifically highlight the unique advantages of Synlogic’s approach to stimulate the innate immune system.
Corporate

Successfully completed two public offerings of common stock in January and April, resulting in approximately $83 million in total net proceeds.
The Company announced executive leadership changes including the appointment of Aoife Brennan, M.B., B.Ch., as president and chief executive officer, and the appointment of Antoine Awad as Head of Technical Operations.
Synlogic expanded its manufacturing capabilities to enable production of clinical trial material for its oral and immuno-oncology programs via entry into an agreement to lease GMP clean-room space from the Azzur Group, LLC. The agreement provides the Company with infrastructure that enables advancement of clinical programs through early and mid-phase studies and supports the production of both solid and oral formulations.
Advanced collaboration with AbbVie to develop Synthetic Biotic-based treatments for IBD resulting in payment to Synlogic of a $2.0 million milestone.
Synlogic was added to both the Russell 3000Index and the NASDAQ Biotechnology Index (Nasdaq: NBI).

On January 3, 2019 Adaptive Biotechnologies reported that Chad Robins, chief executive officer and co-founder, will present at the 37th Annual J.P. Morgan Healthcare Conference on January 8, 2019 at 11:30 am PT (2:30 pm ET) in San Francisco (Press release, Adaptive Biotechnologies, JAN 3, 2019, View Source [SID1234532413]). Robins will also participate in a panel presentation, Reinventing the Disease Continuum Through Precision Health, on January 7, 2019 at 5:00 pm PT (8:00 pm ET) to discuss the impact of immune profiling on the future of immune-driven medicine.

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A live webcast of the presentation and Q&A session can be accessed from the Newsroom under Events on the Adaptive website at adaptivebiotech.com. Following the live presentation, a replay of the webcast will be available on the Company’s website for 90 days.

On January 3, 2019 Sutro Biopharma, Inc. (NASDAQ: STRO) reported that Bill Newell, Chief Executive Officer, will present at the 37th Annual J.P. Morgan Healthcare Conference on Thursday, Jan. 10, 2019 at 11:30 a.m. PT / 2:30 p.m. ET at the Westin St. Francis Hotel in San Francisco (Press release, Sutro Biopharma, JAN 3, 2019, View Source [SID1234532429]).

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A live webcast of the presentation will be accessible through the Events and Presentations page of the Investor Relations section of the company’s website at www.sutrobio.com. A replay of the webcast will be available for approximately 30 days following the event.

On January 3, 2019 Sesen Bio, Inc. (Nasdaq: SESN), a late-stage clinical company advancing targeted fusion protein therapeutics for the treatment of cancer, reported positive preliminary efficacy data for the primary endpoint of its ongoing Phase 3 registration trial, the VISTA Trial, of Vicinium for the treatment of patients with high-grade non-muscle invasive bladder cancer (NMIBC) who have been previously treated with bacillus Calmette-Guérin (BCG) and deemed BCG-unresponsive (Press release, Eleven Biotherapeutics, JAN 3, 2019, View Source [SID1234532380]). The data reported show clinically meaningful complete response rates in evaluable Carcinoma in situ patients at three, six, nine and 12 months of follow-up in the trial consistent with the data in the completed Phase 1 and Phase 2 clinical trials. Importantly, Vicinium continues to be generally well-tolerated in treated patients.

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"Non-muscle invasive bladder cancer is a very prevalent cancer that can progress to become incurable. The usual treatment for patients who relapse or become refractory to BCG, today’s standard-of-care, is complete bladder removal or radical cystectomy," said Michael A.S. Jewett, M.D., Professor of Surgery, Division of Urology, University of Toronto. "Removing the bladder is a potentially morbid and complex surgery with potential for side effects that can drastically reduce a patient’s quality of life. In fact, many patients choose not to undergo bladder removal. I am very encouraged by the data generated to-date with intravesical Vicinium as an alternative after BCG failure. Based on the strength of the clinical activity observed, and the consistently favorable safety and tolerability, I believe that Vicinium has the potential to change the treatment outcome for patients."

VISTATrial Design
The Phase 3 VISTA Trial is a single-arm, multi-center clinical trial designed to support the approval of Vicinium for the treatment of patients with high-grade, BCG-unresponsive NMIBC. The trial enrolled a total of 133 patients across three cohorts based on histology and time to disease recurrence after adequate BCG:

Cohort 1 (n=86): Carcinoma in situ patients with or without papillary disease whose cancer was determined to be refractory or recurred within six months of their last course of adequate BCG
Cohort 2 (n=7): Carcinoma in situ patients with or without papillary disease whose cancer was determined to be refractory or recurred after six months, but less than 12 months, after their last course of adequate BCG
Cohort 3 (n=40): patients with papillary disease without Carcinoma in situ whose cancer was determined to be refractory or recurred within six months of their last course of adequate BCG
The data reported build upon preliminary three-month data presented from a subset of patients in May 2018 and are for the primary endpoint of the VISTA Trial, which is the complete response rate and duration of response in patients in Cohort 1. The company also reported data from Cohort 2, separately and pooled with Cohort 1, based on final U.S. Food and Drug Administration guidance on treatment of BCG-unresponsive Carcinoma in situ patients (defined as patients with recurrent Carcinoma in situ within 12 months of adequate BCG therapy)1.

The patient population in Cohort 3 represents an opportunity for future label expansion, and the company plans to report efficacy data from this cohort, as well as the secondary endpoints in the VISTA Trial, in mid-2019.

Preliminary Efficacy Results in Carcinoma in situ Patients

Cohort 1 (n=86)

Time point Evaluable Patients Complete Response Rate (95% Confidence Interval)
3-months n=86 37% (27%, 48%)
6-months n=85 25% (16%, 35%)
9-months n=84 18% (10%, 28%)
12-months n=81 14% (7%, 23%)

Cohort 2 (n=7)

Time point Evaluable Patients Complete Response Rate (95% Confidence Interval)
3-months n=7 57% (18%, 90%)
6-months n=7 57% (18%, 90%)
9-months n=7 43% (10%, 82%)
12-months n=7 14% (0%, 58%)

Pooled Cohorts 1 and 2 (n=93)

Time point Evaluable Patients Complete Response Rate (95% Confidence Interval)
3-months n=93 39% (29%, 49%)
6-months n=92 27% (18%, 37%)
9-months n=91 20% (12%, 29%)
12-months n=88 14% (7%, 23%)

Notably, the interim Phase 3 complete response rates in pooled patients from Cohorts 1 and 2 are in-line with the complete response rates in pooled patients in the completed Phase 2 clinical trial.

Preliminary Phase 3 CRR vs Phase 2 CRR

Time point Phase 3 Pooled CRR
(95% Confidence Intervals)

Phase 2 Pooled CRR
(95% Confidence Interval)

3-months 39% (29%, 49%) 40% (26%, 56%)
6-months 27% (18%, 37%) 27% (15%, 42%)
9-months 20% (12%, 29%) 18% (8%, 32%)
12-months 14% (7%, 23%) 16% (7%, 30%)

The company also reported an update on the durability of responses in the VISTA Trial. While the median has not yet been reached, the preliminary data show that Vicinium treatment resulted in a prolonged duration of response in many patients. This is particularly notable given that, in order for patients to remain on study, they have to have achieved a complete response at each assessment time period. These findings suggest that Vicinium has the potential to benefit patients by delaying the time to a radical cystectomy, a secondary endpoint that will be measured and reported in mid-2019.

Preliminary Safety Results
Vicinium continues to be well-tolerated by patients treated in the VISTA Trial. As of the December 3, 2018 data cut off, in patients across all three cohorts (n=133), 78 percent of adverse events were Grade 1 or 2. The most commonly reported treatment-related adverse events were dysuria (13%), hematuria (12%) and urinary tract infection (11%) – all of which are consistent with the profile of bladder cancer patients and the use of catheterization for treatment delivery. These adverse events were determined to be manageable and reversible, and only five patients discontinued treatment due to an adverse event. Serious adverse events, regardless of treatment attribution, were reported in 14 percent of patients. There were four treatment-related SAEs reported in three patients including acute renal injury (Grade 3), pyrexia (Grade 2), cholestatic hepatitis (Grade 4) and renal failure (Grade 5).

"We are very pleased with these preliminary data, which are consistent with the data in our completed Phase 2 clinical trial of Vicinium for the treatment of high-grade NMIBC, and further support our belief that Vicinium has the potential to change how patients are treated after BCG," said Dr. Thomas Cannell, president and chief executive officer of Sesen Bio. "The design of the VISTA Trial aligns with FDA’s guidance for NMIBC drug development, and the findings are highly encouraging, demonstrating that treatment with Vicinium results in clinically meaningful efficacy and favorable safety and tolerability. Overall, the data reinforce our belief that Vicinium is positioned to provide a valuable benefit to patients by treating their disease with long-term responses and extending their time to face such a decision as removing their bladder. 2019 is set to be a transformational year for Sesen Bio, and we look forward to advancing the VISTA Trial and assessing the full 12-month data from all patients later this year."

The VISTA Trial completed enrollment in the second quarter of 2018, and complete 12-month efficacy data from all patients in the clinical trial are expected to be reported at a medical meeting in mid-2019.

Conference Call Information
To participate in the conference call, please dial (844) 831-3025 (domestic) or (315) 625-6887 (international) and refer to conference ID 4263106. The webcast can be accessed in the Investor Relations section of the company’s website at www.sesenbio.com. The replay of the webcast will be available in the investor section of the company’s website at www.sesenbio.com for 60 days following the call.

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 in patients with high-grade non-muscle invasive bladder cancer (NMIBC) that is Carcinoma in situ, which is cancer found on the inner lining of the bladder that has not spread into muscle or other tissue and/or papillary, which is cancer that has grown from the bladder lining out into the bladder but has not spread into muscle or other tissue, who have been previously treated with bacillus Calmette-Guérin (BCG). The primary endpoint of the trial is the complete response rate 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. Twelve-month data from all patients in the VISTA Trial are anticipated in mid-2019. 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-grade 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 (ETA). 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 Sesen Bio, EpCAM has been shown to be overexpressed in NMIBC cells with minimal to no EpCAM expression observed on normal bladder cells. Sesen Bio is currently conducting the Phase 3 VISTA Trial, designed to support the registration of Vicinium for the treatment of high-grade NMIBC in patients who have previously received two courses of bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. Complete twelve-month data from the trial are anticipated in mid-2019. Additionally, Sesen Bio believes that Vicinium’s cancer cell-killing properties promote an anti-tumor immune response that may potentially combine well with immuno-oncology drugs, such as checkpoint inhibitors. The activity of Vicinium in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.

About Non-Muscle Invasive Bladder Cancer
Bladder cancer is the sixth most commonly diagnosed cancer in the United States, and approximately 80 percent of patients have non-muscle invasive bladder cancer (NMIBC). In NMIBC, cancer cells are in the lining of the bladder or have grown into the lumen of the bladder but have not spread into muscle or other tissue. NMIBC primarily affects men and is associated with carcinogen exposure. Initial treatment includes surgical resection; however, there is a high rate of recurrence and more than 60 percent of all patients diagnosed with NMIBC will receive bacillus Calmette-Guérin (BCG) immunotherapy. While BCG is effective in many patients, challenges with tolerability have been observed and many patients will experience recurrence of disease. If BCG is not effective or a patient can longer receive BCG, the recommended option for treatment is radical cystectomy, the complete removal of the bladder.

On January 3, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported that its CEO, Jan van de Winkel, Ph.D., will present a company update at the 37th Annual J.P. Morgan Healthcare Conference in San Francisco at 3:30 PM PST on January 9, 2019 (12:30 AM CET, January 10) (Press release, Genmab, JAN 3, 2019, View Source [SID1234532397]). A webcast of the presentation will be available on Genmab’s website at View Source

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