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]).

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!

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 ANI Pharmaceuticals, Inc. (NASDAQ: ANIP) ("ANI" or the "Company") reported the pricing of an underwritten public offering of 1,500,000 shares of its common stock at a public offering price of $50.00 per share (Press release, ANI Pharmaceuticals, NOV 3, 2021, View Source [SID1234594277]). The gross proceeds of the offering to the Company are expected to be $75 million, before deducting the underwriting discounts and commissions and other offering expenses. In addition, ANI granted the underwriters a 30-day option to purchase up to an additional 225,000 shares of common stock at the public offering price, less underwriting discounts and commissions.

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 closing of the offering is expected to occur on or about November 8, 2021, subject to the satisfaction of customary closing conditions.

Guggenheim Securities is acting as lead book-running manager for the offering. Raymond James is also acting as book-running manager for the offering. H.C. Wainwright & Co. is acting as lead manager for the offering.

The securities described above are being offered by ANI pursuant to a shelf registration statement on Form S-3 (File No. 333-239771) which was initially filed by the Company with the Securities and Exchange Commission (the "SEC") on July 9, 2020 and was declared effective by the SEC on July 17, 2020.

A preliminary prospectus supplement relating to the offering was filed with the SEC on November 3, 2021 and is available on the SEC’s website at View Source The final prospectus supplement relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website. Before investing in the offering, you should read each of the prospectus supplement and the accompanying prospectus relating to the offering in their entirety as well as the other documents that the Company has filed with the SEC that are incorporated by reference in the prospectus supplement and the accompanying prospectus relating to the offering, which provide more information about the Company and the offering. Copies of the final prospectus supplement, when available, and accompanying prospectus relating to the offering may be obtained from Guggenheim Securities, LLC Attention: Equity Syndicate Department, 330 Madison Avenue, New York, NY 10017 or by telephone at (212) 518-9544, or by email at [email protected], and from Raymond James & Associates, Inc. Attention: Equity Syndicate, 880 Carillon Parkway, St. Petersburg, Florida 33716, by telephone at (800) 248-8863 or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On November 3, 2021 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, and The Royal Marsden NHS Foundation Trust, one of the United Kingdom’s (UK) leading cancer research organizations, reported that they have agreed to enter into a partnership to establish an in-house liquid biopsy testing service using Guardant Health’s industry-leading proprietary digital sequencing platform (Press release, Guardant Health, NOV 3, 2021, View Source [SID1234594275]).

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 service is expected to become operational at the end of 2022 and will be available for clinical research and clinical care. This will be the first UK hospital for Guardant Health to house a dedicated liquid biopsy testing facility for cancer diagnostics.

"We are delighted to announce this partnership with Guardant Health, establishing a state-of-the-art liquid biopsy testing facility. In a clinical diagnostic setting, it will provide many of our patients with more rapid access to bespoke diagnostic testing, leading to earlier, faster, and more accurate diagnosis, along with targeted treatment selection and monitoring," said Professor Michael Hubank, Director of Clinical Genomics (Research) at The Royal Marsden NHS Foundation Trust. "The opening of this service will also allow us to significantly increase our capacity for research using liquid biopsies. Bringing expanded capacity for genomic testing, the facility will help us identify more people with cancer for clinical trials based on targeted treatments, improving outcomes for patients across the UK and beyond."

It is estimated that there were around 375,000 new cancer cases in the UK from 2016-20181, with approximately 166,000 cancer deaths in the UK from 2016-2018.1 Guardant Health’s tests are used by oncologists around the world to guide treatment decisions across solid tumor cancers, and by pharmaceutical companies and academic researchers in clinical trials to accelerate precision medicine drug development. Guardant Health has achieved CE Mark and U.S. Food and Drug Administration approval for its Guardant360 CDx assay for tumor mutation profiling, also known as comprehensive genomic profiling (CGP), in patients with any solid cancerous tumor.

"We are pleased to announce this partnership with The Royal Marsden NHS Foundation Trust, which will enable clinicians to quickly and accurately detect relevant tumor alterations with a blood test to guide personalized treatment plans and provide researchers with diagnostic tools to support clinical research and innovation," said Helmy Eltoukhy, Guardant Health Co-CEO. "This partnership further advances our goal of ensuring all patients with cancer have access to the latest innovations to inform their treatment management to enable the best possible outcomes."

On November 3, 2021 ANI Pharmaceuticals, Inc. (NASDAQ: ANIP) ("ANI") reported that it intends to offer and sell shares of its common stock in an underwritten public offering (Press release, ANI Pharmaceuticals, NOV 3, 2021, View Source [SID1234594274]). All of the shares to be sold in the offering will be offered by ANI. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering. In addition, ANI intends to grant the underwriters a 30-day option to purchase up to an additional 15% of shares of its common stock offered in the public offering.

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!

Guggenheim Securities is acting as book-running manager.

ANI anticipates using the net proceeds from the offering to fund its Cortrophin commercialization efforts, including, but not limited to, sales and marketing and consulting expenses related thereto, and for general corporate purposes. We may also use a portion of the net proceeds to in-license, acquire or invest in additional businesses, technologies, products or assets.

The securities described above are being offered by ANI pursuant to a shelf registration statement on Form S-3 (File No. 333-239771) which was initially filed by the Company with the Securities and Exchange Commission (the "SEC") on July 9, 2020, and was declared effective by the SEC on July 17, 2020.

The securities will be offered only by means of a prospectus supplement and accompanying prospectus relating to the offering that form a part of the registration statement. A preliminary prospectus supplement and the accompanying prospectus relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website at View Source Copies of the final prospectus supplement, when available, and accompanying prospectus relating to the offering may be obtained from Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, New York, NY 10017, by telephone at (212) 518-9544, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On November 3, 2021 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported updated clinical data from a Phase 1 study of tidutamab, an SSTR2 x CD3 bispecific antibody, in patients with neuroendocrine tumors (NETs) (Press release, Xencor, NOV 3, 2021, View Source [SID1234594273]). The data will be presented during the North American Neuroendocrine Tumor Society’s 2021 Multidisciplinary NET Medical Virtual Symposium (NANETS).

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 Phase 1 study of tidutamab in patients with neuroendocrine tumors informed our view that an XmAb CD3 bispecific antibody is generally well tolerated in solid tumors, with a low incidence and severity of CRS, and can induce meaningful biological activity in a challenging disease setting," said Allen Yang, M.D., Ph.D., senior vice president and chief medical officer at Xencor. "Importantly, we identified a recommended dose for continued study, and a Phase 1b/2 study has been opened to evaluate tidutamab as a potential treatment option for patients with Merkel cell carcinoma and small cell lung cancer, SSTR2-expressing tumor types known to be responsive to immunotherapy."

A poster with data from the study is available in the NANETS Virtual Poster Hall, and it will be made available under Archived Scientific Presentations on the Events & Presentations page in the Investors section of www.xencor.com. In addition to the poster, these results will be presented during the Clinical Abstracts session, which begins at 1:25 p.m. ET on Saturday, November 6, 2021.

Key Highlights

The primary objectives of the Phase 1 study were to determine the safety and tolerability profile of tidutamab in patients with advanced, well-differentiated NETs of pancreatic, gastrointestinal, lung and undetermined origin, and to identify the maximum tolerated dose and/or recommended dosing regimen for continued study, which was determined to be a 0.3 mcg/kg priming dose followed by 1.0 mcg/kg on subsequent dosing days.

At data cut-off in August 2021, 41 patients with neuroendocrine tumors, with the initial lesion location in the pancreas (46%), intestine (22%), lung (20%), and other GEP-NET or unknown (12%), received doses of tidutamab ranging from 0.1 to 2.0 mcg/kg. Dosing in the study included a lower priming dose, followed by a higher repeated dose on subsequent dosing days. The 20 patients in the expansion cohort received the recommended dosing regimen. Patients had a median age of 64 years and a median of four prior lines of systemic therapies. Fifty percent of patients received prior peptide receptor radionuclide therapy.

Tidutamab was generally well tolerated at the 0.3/1.0 mcg/kg dose identified for the expansion portion of the study. All 41 patients treated were included in the safety analysis. The most common treatment-related Grade 3 or Grade 4 adverse events across all doses were lymphopenia (29%), gamma-glutamyl transferase increases (20%), transaminase increases (20%) and vomiting (17%). In addition, Grade 3 esophageal dysmotility was observed in 7% of patients. CRS of any grade was observed in 41% of patients. The majority of CRS was limited to Grade 1 and Grade 2 and to the first two doses. Grade 3 CRS was observed in two patients (5%) upon the first dose. All patients experiencing CRS fully recovered.

Analysis of peripheral blood biomarkers indicated that tidutamab induced acute and sustained T-cell activation at the recommended dose for expansion. CD8-positive effector T cells showed a dose-dependent increase in proliferation (Ki67) and activation (PD-1) markers that began within 48 hours of the first dose and persisted at least seven weeks, as measured at cycle 2, day 22.

The best overall response was stable disease, with a disease control rate of 27%. Higher tumor PD-L1 expression was associated with a shorter time on study, and the patients with prolonged stable disease were most likely to have low or absent PD-L1 expression, suggesting a potential beneficial effect from the combination of tidutamab with PD-L1 inhibitors.

About Tidutamab

Tidutamab is a tumor-targeted bispecific antibody that contains both an SSTR2 binding domain and a T-cell binding domain (CD3). An XmAb bispecific Fc domain serves as the scaffold for the two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on tidutamab. SSTR2 (somatostatin receptor 2) is an antigen highly expressed on some solid tumors, and engagement of CD3 by tidutamab activates T cells for highly potent and targeted killing of SSTR2-expressing tumor cells. Tidutamab is being evaluated in an ongoing Phase 1b/2 study, which is enrolling patients with Merkel cell carcinoma and small cell lung cancer, SSTR2-expressing tumor types known to be responsive to immunotherapy.