On November 3, 2021 Synthetic Biologics, Inc. (NYSE American: SYN), a diversified clinical-stage company leveraging the microbiome to develop therapeutics designed to prevent and treat gastrointestinal ("GI") diseases in areas of high unmet need, reported financial results for the third quarter ended September 30, 2021 (Press release, Synthetic Biologics, NOV 3, 2021, View Source [SID1234594278]).

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Recent Developments:

Initiated a Phase 1, placebo-controlled, multiple ascending dose clinical study of SYN-020 intestinal alkaline phosphatase ("IAP")
Continuing enrollment in the Phase 1b/2a clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant ("HCT") recipients
Current cash position of approximately $72.1 million
Current cash runway expected to provide funding to complete Phase 1b/2a clinical trial of SYN-004, clinical trials of SYN-020 through proof-of-concept, and other key milestones into 2023
Anticipated Milestones:

Topline data readout from the first antibiotic cohort of the SYN-004 Phase 1b/2a clinical trial is expected during Q1 2022
Expect to announce topline data readout from the Company’s Phase 1 MAD clinical trial of SYN-020 during Q2 2022
"During the third quarter, we significantly advanced our portfolio of GI and microbiome-focused clinical programs," said Steven A. Shallcross, Chief Executive Officer of Synthetic Biologics. "We were pleased to initiate a Phase 1 multiple ascending dose clinical trial of our SYN-020 IAP program during the third quarter of 2021. At this time, the first cohort of 8 study participants is nearing completion with dosing of the second cohort of 8 study participants expected to begin shortly thereafter, pending a safety review. We anticipate reporting topline data from this clinical trial during the second quarter of 2022. This study follows our recent Phase 1 single ascending dose ("SAD") clinical trial of SYN-020, in which SYN-020 was well tolerated and demonstrated a favorable safety profile at all doses. Both clinical trials are designed to support the advancement of SYN-020 in multiple potential therapeutic indications, including radiation enteropathy, celiac disease, non-alcoholic fatty liver disease (NAFLD), and age-related metabolic and inflammatory diseases. We continue to view SYN-020 as a multi-indication platform program, which has the potential to help address a considerable need for innovative new therapies targeting disorders that stem from immune and inflammatory damage to the intestine."

Mr. Shallcross continued, "We also continue to progress the SYN-004 Phase 1b/2a clinical trial in allogeneic hematopoietic cell transplant ("HCT") recipients. Patient screening and enrollment is ongoing at the Washington University School of Medicine in St. Louis ("Washington University"). As a result, we currently anticipate announcing topline results from the first of three antibiotic cohorts during the first quarter of 2022. We believe SYN-004 has the potential to address a significant unmet medical need by improving outcomes for allogeneic HCT recipients. Overall, we remain very excited about the potential for each of our clinical programs and near-term clinical milestones that we believe could drive significant value for shareholders."

Clinical Development and Operational Update

Announced commencement of the Company’s Phase 1, placebo-controlled, multiple ascending dose clinical trial of SYN-020
The ongoing Phase 1 MAD clinical trial is intended to evaluate the safety, tolerability and biodistribution of SYN-020 upon repeated dosing in up to 32 healthy adult volunteers.
The study is divided into 4 sequential cohorts of 8 participants, with SYN-020 (5 mg, 15, mg, 45 mg or 75 mg) given orally twice daily for 14 days.
At this time, the first cohort of 8 study participants is nearing completion and dosing of the second cohort of 8 study participants is expected to begin shortly thereafter, pending a safety review.
A safety review will be conducted at the end of each cohort to determine whether progression to the next higher dose cohort is permissible.
A topline data readout from this clinical trial is anticipated during the second quarter of 2022, pandemic conditions permitting.
A previously completed Phase 1 single ascending dose clinical study of SYN-020 enrolled 24 healthy adult volunteers into four cohorts with SYN-020 given orally as a single dose ranging from 5 mg to 150 mg. Analyses of preliminary data demonstrated that SYN-020 maintained a favorable safety profile, was well tolerated at all dose levels, and no adverse events were attributed to study drug. No serious adverse events were reported.
Both studies are intended to support the development of SYN-020 in multiple potential clinical indications including radiation enteropathy, celiac disease, NAFLD, as well as indications supported by the Company’s collaboration with Massachusetts General Hospital.
Enrollment in the Company’s Phase 1b/2a clinical trial of SYN-004 in allogeneic HCT recipients for the prevention of acute graft-versus-host-disease ("aGVHD") remains ongoing
The Phase 1b/2a clinical trial comprises a single center, randomized, double-blind, placebo-controlled clinical trial of oral SYN-004 in up to 36 evaluable adult allogeneic HCT recipients.
The goal of this clinical trial is to evaluate the safety, tolerability, and potential absorption into the systemic circulation (if any) of oral SYN-004 administered to allogeneic HCT recipients who receive an IV beta-lactam antibiotic to treat fever.
Study participants will be enrolled into three sequential cohorts and administered a different study-assigned IV beta-lactam antibiotic. Eight participants in each cohort will receive SYN-004 and 4 will receive placebo.
Safety and pharmacokinetic data for each cohort will be reviewed by an independent Data and Safety Monitoring Committee ("DSMC"), which will make a recommendation on whether to proceed to the next IV beta-lactam antibiotic.
A topline data readout for the first of three antibiotic cohorts is anticipated during the first quarter of 2022, pandemic conditions permitting.
Quarter Ended September 30, 2021 Financial Results

General and administrative expenses increased by 9% to approximately $1.3 million for the three months ended September 30, 2021, from approximately $1.2 million for the three months ended September 30, 2020. This increase is primarily due to higher insurance costs, audit fees and registration fees offset by lower legal costs and vacation expense. The charge related to stock-based compensation expense was $83,000 for the three months ended September 30, 2021, compared to $67,000 for the three months ended September 30, 2020.

Research and development expenses increased by 116% to approximately $2.0 million for the three months ended September 30, 2021, from approximately $900,000 for the three months ended September 30, 2020. This increase is primarily the result of increased clinical trial expenses as we continued dosing patients in the Phase 1b/2a clinical trial of SYN-004 and by higher indirect program costs for the three months ended September 30, 2021, including an increase in manufacturing costs for SYN-020. We anticipate research and development expense to increase as our ongoing clinical trials continue to enroll patients. The charge related to stock-based compensation expense was $19,000 for the three months ended September 30, 2021, compared to $15,000 related to stock-based compensation expense for the three months ended September 30, 2020.

Other income was $2,000 for the three months ended September 30, 2021, compared to other income of $134 for the three months ended September 30, 2020. Other income for the three months ended September 30, 2021 and 2020 is primarily comprised of interest income.

Cash and cash equivalents as of September 30, 2021 totaled $72.1 million, an increase of $65.9 million from December 31, 2020.

Conference Call

Synthetic Biologics will hold a conference call today, Wednesday, November 3, 2021, at 4:30 p.m. (EST). The dial-in information for the call is as follows, U.S. toll free: 1-888-347-5280 or International: +1 412-902-4280. Participants are asked to dial in 15 minutes before the start of the call to register. The call will also be webcast over the Internet at View Source." target="_blank" title="View Source." rel="nofollow">View Source An archive of the call will be available for replay at the same URL, View Source, for 90 days after the call.

On November 3, 2021 Merus N.V. (Nasdaq: MRUS) ("Merus", the "Company," "we", or "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported a regulatory update for the zenocutuzumab (Zeno) program in NRG1 positive (NRG1+) solid tumors, financial results for the third quarter that ended September 30, 2021, and provided a business update (Press release, Merus, NOV 3, 2021, View Source [SID1234594295]).

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"Our recent regulatory interactions with the FDA demonstrate the maturation of the Zeno program as we continue on the path to potential BLA submission," said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. "In addition, with MCLA-158, we are also encouraged by the early interim clinical data we recently reported in head and neck cancer, and the continued progress of our other clinical programs. We believe the positive results we are seeing in the clinic further validate the strength of our platform."

Clinical Programs

Zenocutuzumab (Zeno or MCLA-128: HER3 x HER2 Biclonics)

Alignment obtained with the FDA on registration approach for a potential tumor agnostic indication: clinical update planned for 1H22

Merus met with the U.S. Food and Drug Administration (FDA) in an end-of-phase Type B meeting to discuss interim results from the ongoing phase 1/2 eNRGy trial and Early Access Program (EAP) in NRG1+ cancers, and to discuss the development plan for Zeno. Merus and the FDA officials discussed the available Zeno monotherapy data and a potential data package to support a biologics license application (BLA) submission.

Merus designed the phase 1/2 eNRGY trial to support potential registration in either a tumor-specific or a tumor agnostic NRG1+ indication(s). Based on feedback received from the FDA, Merus believes that the trial design and planned enrollment will be appropriate to potentially support a BLA submission seeking a tumor agnostic indication for Zeno in patients with previously treated NRG1+ cancers. Merus believes that, if the rate of enrollment and efficacy remains consistent, a sufficient number of patients will be enrolled in the eNRGy trial and EAP, with sufficient follow up, by mid-2022, that could provide a potential registrational data set.

Andrew Joe, M.D., Chief Medical Officer of Merus, stated, "We are very pleased with our recent regulatory interactions including alignment with the FDA on a tumor agnostic approach for NRG1+ cancers, for which Zeno has already received Fast Track designation. Regulatory interactions such as these represent continued progress in Merus’ mission to bring our novel multispecific antibody therapy candidates to patients with serious unmet medical need."

As of September 1, 2021 more than 80 patients with NRG1+ cancers have been treated with Zeno monotherapy in our phase 1/2 eNRGy trial and EAP. Merus plans to provide a further clinical program update in the first half of 2022.

Details of the eNRGy trial can be found at www.ClinicalTrials.gov and Merus’ trial website at www.nrg1.com, or by calling 1-833-NRG-1234.

In addition, we presented preclinical data on Zeno at the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). The bispecific HER2/HER3 antibody Zeno blocked cell growth 100 fold more potently than the bivalent HER3 antibody derived from Zeno, in an NRG1 driven growth assay, and potently blocked NRG1-fusion mediated downstream signaling and growth in in vitro and in vivo models. Zeno induced both antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) mediated killing of cancer cells in a dose-dependent manner.

MCLA-158 (petosemtamab: Lgr5 x EGFR Biclonics): Solid Tumors

Dose expansion continues in the phase 1 trial: update planned for 2022

We shared early interim clinical data of the MCLA-158 program in patients with advanced HNSCC at the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). Among 10 patients with previously treated advanced HNSCC, as of the August 9, 2021 safety and efficacy data cutoff, the median age was 65 and the median number of prior lines of therapy was two. Seven patients were evaluable for an interim efficacy analysis by investigator assessment (three patients were enrolled <8 weeks from the data cutoff date). Three of seven patients achieved a best response of partial response, with one achieving complete response after the data cutoff date. Tumor reduction was observed in the target lesions of all seven patients. The safety results presented for MCLA-158 were based on 29 patients with advanced solid tumors who were treated at 1500 mg every two weeks across the phase 1 trial. The most frequent adverse events (AEs) were infusion related reactions with 72% any grade and 7% grade 3 or greater. Mild to moderate skin toxicity (3% grade ≥3) was also observed.

MCLA-145 (CD137 x PD-L1 Biclonics): Solid Tumors

Phase 1 trial continues: update planned for ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2021

The phase 1, open-label, single-agent clinical trial of MCLA-145 is ongoing. The trial consists of a dose escalation phase, to be followed by a planned dose expansion phase. MCLA-145 is the first drug candidate co-developed under Merus’ global collaboration and license agreement with Incyte Corporation ("Incyte"), which permits the development and commercialization of up to 11 bispecific and monospecific antibodies from the Merus Biclonics platform. Merus retains full rights to develop and commercialize MCLA-145, if approved, in the United States; and Incyte holds full rights to develop and commercialize MCLA-145 outside the United States. We plan to provide an update at ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2021.

MCLA-129 (EGFR x c-MET Biclonics): Solid Tumors

The phase 1/2, open-label, single-agent clinical trial of MCLA-129 is ongoing and consists of a dose escalation phase, to be followed by planned expansion cohorts evaluating MCLA-129 for the treatment of patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors. MCLA-129 is a Biclonics, which binds to EGFR and c-MET and is being investigated for the treatment of solid tumors. EGFR is an important oncogenic driver in many cancers, and upregulation of c-MET signaling has been associated with resistance to EGFR inhibition. We plan to provide an update after the recommended phase 2 dose has been reached.

MCLA-129 is subject to a collaboration and license agreement with Betta Pharmaceuticals Co. Ltd. (Betta), which permits Betta to exclusively develop MCLA-129 in China, while Merus retains full ex-China rights.

In October 2021, Betta announced that the first patient was dosed in Betta’s sponsored phase 1/2 trial of MCLA-129 in China in patients with advanced solid tumors.

Collaborations Update

Incyte

In the third quarter Merus received a milestone payment for achieving pre-clinical candidate nomination of a novel bispecific antibody (target pair program) under the global collaboration and license agreement with Incyte. Candidate nomination has triggered this program’s next phase of IND-enabling studies by Incyte.

Merus receives reimbursement for research activities related to the collaboration and is eligible to receive potential development, regulatory and commercial milestones and sales royalties for any products, if approved.

Loxo Oncology at Lilly

In January 2021 Merus and Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company (Lilly) announced a research collaboration and exclusive license agreement that will leverage Merus’ proprietary Biclonics platform along with the scientific and rational drug design expertise of Loxo Oncology at Lilly to research and develop up to three CD3-engaging T-cell re-directing bispecific antibody therapies. The collaboration is progressing well with active research programs underway.

Third Quarter 2021 Financial Results

We ended the third quarter with cash, cash equivalents and marketable securities of $333.2 million compared to $207.8 million at December 31, 2020. The increase was primarily the result of net proceeds from our follow-on offering and proceeds from the collaboration with and equity investment by Eli Lilly and Company ("Lilly"), net of cash used in operations and other items. Based on the Company’s current operating plan, we expect that our existing cash and cash equivalents and marketable securities of $333.2 million as of September 30, 2021, will fund the Company’s operations into the second half of 2024.

Collaboration revenue for the three months ended September 30, 2021 increased by $5.1 million as compared to the three months ended September 30, 2020, primarily as a result of an increase from a Lilly upfront payment amortization and reimbursement revenues of $5.0 million that commenced in the first quarter of 2021. The change in exchange rates did not significantly impact collaboration revenue.

Research and development expense for the three months ended September 30, 2021 increased by $8.5 million as compared to the three months ended September 30, 2020, primarily as a result of an increase in clinical and manufacturing costs related to our programs and stock-based compensation.

General and administrative expense for the three months ended September 30, 2021 increased by $1.1 million as compared to the three months ended September 30, 2020, primarily as a result of an increase in stock-based compensation and other personnel related expenses, partially offset by decreases in legal and depreciation costs.

Collaboration revenue for the nine months ended September 30, 2021 increased by $13.5 million as compared to the nine months ended September 30, 2020, primarily as a result of an increase from a Lilly upfront payment amortization and reimbursement revenues of $11.0 million that commenced in the first quarter of 2021, and $1.0 million of milestone revenue related to Incyte reflecting activities in the period. The change in exchange rates did not significantly impact collaboration revenue.

Research and development expense for the nine months ended September 30, 2021 increased by $23.2 million as compared to the nine months ended September 30, 2020, primarily as a result of an increase in clinical and manufacturing costs related to our programs and stock-based compensation.

General and administrative expense for the nine months ended September 30, 2021 increased by $4.0 million as compared to the nine months ended September 30, 2020, primarily as a result of an increase in stock-based compensation and other personnel related expenses partially offset by decreases in legal and IP related costs and travel expenses.

Other income (loss), net consists of interest earned and fees paid on our cash and cash equivalents held on account, accretion of investment earnings and net foreign exchange (losses) gains on our foreign denominated cash, cash equivalents and marketable securities. Other gains or losses relate to the issuance and settlement of financial instruments.

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On November 3, 2021 Genmab A/S (Nasdaq: GMAB) reported that its CEO, Jan van de Winkel, Ph.D., will take part in a fireside chat at the Jefferies Virtual London Healthcare Conference on November 18, 2021 (Press release, Genmab, NOV 3, 2021, View Source [SID1234594205]). A webcast of the event will be available on Genmab’s website from November 18, 2021, 9:00 AM CET at View Source

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On November 3, 2021 CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, reported that it will host a conference call and live audio webcast on Wednesday, November 10, 2021 at 4:30 p.m. Eastern Time to discuss financial results for the third quarter ended September 30, 2021 and to provide a business update (Press release, CymaBay Therapeutics, NOV 3, 2021, View Source [SID1234594222]).

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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

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Conference Call Details
To access the live conference call, please dial 877-407-0784 from the U.S. and Canada, or 201-689-8560 internationally, Conference ID# 13723498. To access the live and subsequently archived webcast of the conference call, go to the Investors section of the company’s website at View Source