On August 8, 2019 Synthetic Biologics, Inc. (NYSE American: SYN), a late-stage clinical company developing therapeutics that preserve the microbiome to protect and restore the health of patients, reported financial results for the three months ended June 30, 2019 (Press release, Synthetic Biologics, AUG 8, 2019, View Source [SID1234538465]). The Company also announced today a clinical trial agreement with Washington University School of Medicine in St. Louis ("Washington University") to conduct a Phase 1b/2a clinical trial of SYN-004 (ribaxamase), with enrollment expected to begin in the first quarter of 2020.

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"Our clinical trial collaboration with Washington University is an important step in our pursuit of a more cost-effective development strategy for SYN-004 targeting a more specialized patient population," stated Steven A. Shallcross, Chief Executive and Financial Officer. "SYN-004’s unique mechanism of action designed to degrade intravenous (IV) beta-lactam antibiotics and prevent dysbiosis of the gut microbiome has the potential to significantly improve outcomes for patients who undergo allogeneic hematopoietic cell transplantation (HCT), an area of significant unmet medical need."

"Prompt initiation of broad-spectrum IV beta-lactam antibiotics at onset of fever after conditioning chemotherapy for allogenic HCT is a life-saving intervention. However, this causes significant disruption of the microbiome, which places these patients at very high risk for infection due to some of our greatest antibiotic resistant threats, such as Clostridioides difficile, vancomycin-resistant Enterococci (VRE), and multidrug-resistant Gram-negative bacteria. We are seeking to determine if coadministration of SYN-004 while the patient is receiving IV beta-lactam antibiotics will preserve the microbiome and thus mitigate the risk from these threats," said Dr. Erik R. Dubberke Professor of Medicine and Clinical Director, Transplant Infectious Diseases at Washington University. "There are data to suggest preservation of the microbiome in allogeneic HCT recipients results in improved immune function after HCT as well. This would further enhance these patients’ outcomes and quality of life."

Mr. Shallcross continued, "During the second quarter, we remained focused on executing our strategy to advance our portfolio of gastrointestinal (GI) and microbiome-focused clinical programs. We held a highly informative pre-IND meeting with the U.S. Food and Drug Administration (FDA) for our SYN-020 intestinal alkaline phosphatase (IAP) program and clarified the parameters for IND-enabling toxicology studies. These activities are ongoing and will support our anticipated Investigational New Drug (IND) application which we intend to file promptly during the first quarter of 2020." Mr. Shallcross concluded, "Interest from prospective patients in our investigator-sponsored Phase 2b clinical trial of SYN-010 in breath-methane positive irritable bowel syndrome with constipation (IBS-C) patients remains strong. However, after consulting with the investigators at Cedars-Sinai Medical Center, the study sponsor, enrollment has been extended to accommodate higher than anticipated screen-fail rates. This is, in part, due to errant laxative use during the screening period that adversely impacts baseline measurements of IBS-C symptoms and breath-methane levels. Rigorous screening and reliable baseline parameters are critical to all IBS-C clinical trials in order to ensure the possibility of generating a meaningful data set of the highest quality. At this time, we are discussing with Cedars-Sinai the opportunity for a data read out in the first half of 2020, extending our previous guidance from the fourth quarter of 2019. We look forward to sharing important updates and progress for this and all our GI and microbiome-focused clinical programs."

Clinical Development and Operational Update

Entered into a Clinical Trial Agreement with Washington University School of Medicine in St. Louis to conduct a Phase 1b/2a clinical trial of SYN-004 (ribaxamase)
Under the terms of this agreement, Synthetic Biologics will serve as the sponsor of the study and supply SYN-004 (ribaxamase) and Dr. Dubberke will serve as the principal investigator along with his Washington University colleague Dr. Mark A. Schroeder, Associate Professor of Medicine, Division of Oncology, Bone Marrow Transplantation and Leukemia,
Enrollment is expected to begin during the first quarter of 2020, contingent upon review by the FDA and approval of the clinical study protocol by Washington University’s Institutional Review Board (IRB),
The proposed study is a Phase 1b/2a single-center, randomized, double-blinded, placebo-controlled clinical trial designed to evaluate the safety, tolerability and pharmacokinetics of oral SYN-004 (ribaxamase) in up to 36 adult allogeneic HCT recipients,
Study participants will be enrolled into three sequential cohorts that will be administered a different study-assigned IV beta-lactam antibiotic. Eight participants in each cohort will receive SYN-004 (ribaxamase) and four will receive placebo,
Safety and pharmacokinetic data for each cohort will be reviewed by an independent Data and Safety Monitoring Committee, which will make a recommendation on whether to proceed to the next IV beta-lactam antibiotic,
The proposed study will also evaluate potential protective effects of SYN-004 (ribaxamase) on the gut microbiome as well as generate preliminary information on potential therapeutic benefits and patient outcomes of SYN-004 (ribaxamase) in allogeneic HCT recipients;
Enrollment is ongoing in the Phase 2b investigator-sponsored clinical study of SYN-010, for the treatment of IBS-C
The Phase 2b clinical study is being conducted by the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai Medical Center and is a 12-week, placebo-controlled, double-blind, randomized clinical trial evaluating two dose strengths of oral SYN-010 (21 mg and 42 mg) in approximately 150 patients diagnosed with IBS-C,
The primary objective for the study will be to determine the efficacy of SYN-010, measured as an improvement from baseline in the weekly average number of complete spontaneous bowel movements (CSBMs) during the 12-week treatment period for SYN-010 21 mg and 42 mg daily doses relative to placebo,
Secondary efficacy endpoints for both dose strengths of SYN-010 will measure changes from baseline in abdominal pain, bloating, stool frequency as well as the use of rescue medication relative to placebo,
A data readout is anticipated in 1H 2020,
Cedars-Sinai Medical Center and Synthetic Biologics are co-funding the study. The patent rights covering the use of SYN-010 are owned by Cedars-Sinai Medical Center and are exclusively licensed by Cedars-Sinai Medical Center to Synthetic Biologics;
Evaluated potential clinical development strategies to advance SYN-020 (intestinal alkaline phosphatase) to and through clinical trials targeting areas of significant unmet medical need, including enterocolitis associated with radiation therapy for cancer
Held Pre-IND meeting with FDA and clarified the requirements for IND-enabling toxicology studies
Exploratory study found SYN-020 enhanced 5-FU tumor treatment in a mouse ectopic colon cancer tumor model. A confirmatory study is ongoing with larger cohort sizes and additional mechanistic endpoints which, if repeated, may allow for further broadening of the clinical development strategy for this program,
Anticipate filing a US IND application in Q1 2020;
Continued to exercise prudent cash management and financial stewardship
Further reduced cash burn, extending projected cash runway to fund operations through at least the end of Q3 2020;
Quarter Ended June 30, 2019 Financial Results

General and administrative expenses decreased by 27% to $1.0 million for the three months ended June 30, 2019, from $1.4 million for the three months ended June 30, 2018. This decrease is primarily due to decreased stock-based compensation expense related to forfeitures and decreased options grants, along with the reduction of investor relations and consulting costs. The charge related to stock-based compensation expense was $59,000 for the three months ended June 30, 2019, compared to $264,000 the three months ended June 30, 2018.

Research and development expenses decreased by 27% to $2.6 million for the three months ended June 30, 2019, from $3.6 million for the three months ended June 30, 2018. This decrease is primarily the result of lower SYN-004 (ribaxamase) indirect program costs for the three months ended June 30, 2019, including salary and related expense reductions resulting from the 2018 restructuring and the fact that no clinical trial activity for SYN-004 (ribaxamase) was ongoing during the quarter, offset by an increase in manufacturing costs for SYN-020. The research and development costs incurred during the quarter were primarily related to the investigator-sponsored Phase 2b clinical study of SYN-010, a potential Phase 1b/2a clinical trial of SYN-004 (ribaxamase) in allogeneic HCT recipients, and the continued development of SYN-020. Research and development expenses also include a charge relating to stock-based compensation expense of $31,000 for the three months ended June 30, 2019, compared to $293,000 for the three months ended June 30, 2018.

Other income was $80,000 for the three months ended June 30, 2019, compared to other income of $789,000 for the three months ended June 30, 2018. Other income for the three months ended June 30, 2019 is primarily comprised of interest income while the three months ended June 30, 2018 is comprised of non-cash income of $783,000 from the change in fair value of warrants. The decrease in the fair value of the warrants was due to the decrease in our stock price.

Cash and cash equivalents as of June 30, 2019 was $21.7 million, a decrease of $7.2 million from December 31, 2018.

Conference Call

Synthetic Biologics will hold a conference call today, Thursday, August 8, 2019, at 4:30 p.m. (ET). 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 August 8, 2019 Dynavax Technologies Corporation (Nasdaq: DVAX), a fully-integrated biopharmaceutical company focused on discovering, developing and commercializing novel vaccines, reported the pricing of an underwritten public offering of 18,525,000 shares of its common stock, 4,840 shares of its newly designated non-voting Series B Convertible Preferred Stock (Series B stock), and warrants to purchase an aggregate of 5,841,250 shares of its common stock (Press release, Dynavax Technologies, AUG 8, 2019, View Source [SID1234538497]). Each share of common stock is being sold together with a warrant to purchase 0.25 of a share of common stock, at a combined price to the public of $3.00 per share of common stock and accompanying warrant. Each share of Series B stock is being sold together with warrants to purchase 250 shares of common stock, at a combined price to the public of $3,000.00 per share of Series B stock and accompanying warrants. Each share of Series B stock will be convertible into 1,000 shares of common stock at the holder’s option, subject to beneficial ownership limitations. All of the warrants being sold in the offering will have an exercise price of $4.50 per share of common stock, will be immediately exercisable upon issuance and will expire on the 30-month anniversary of the date of issuance. The offering is expected to close on or about August 12, 2019, subject to customary closing conditions. The gross proceeds to Dynavax from the offering are expected to be $70.1 million, before deducting underwriting discounts and commissions and other offering expenses payable by Dynavax.

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Cowen and William Blair are acting as joint book-running managers for the offering.

Dynavax anticipates using the net proceeds from the offering to fund activities associated with ongoing commercialization of HEPLISAV-B and for general corporate purposes, including working capital.

The securities described above are being offered by Dynavax pursuant to a shelf registration statement that automatically became effective upon filing with the Securities and Exchange Commission (SEC) on August 8, 2017. A final prospectus supplement and the accompanying prospectus related to the offering will be filed with the SEC and will be available on the SEC’s website located at View Source Copies of the final prospectus supplement and the accompanying prospectus relating to this offering, when available, may be obtained by contacting: Cowen and Company, LLC, Attention: Prospectus Department, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (631) 274-2806; or William Blair & Company, L.L.C., Attention: Prospectus Department, 150 North Riverside Plaza, Chicago, IL 60606, by telephone at (800) 621-0687 or by email at [email protected].

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

On August 8, 2019 Diffusion Pharmaceuticals Inc. (Nasdaq: DFFN), a cutting-edge biotechnology company developing new treatments for life-threatening medical conditions by improving the body’s ability to bring oxygen to the areas where it is needed most, reported financial results for the three and six months ended June 30, 2019 and provided a business update (Press release, Diffusion Pharmaceuticals, AUG 8, 2019, View Source [SID1234538539]).

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During the second quarter of 2019, the Company completed a public offering of 1,317,060 shares of its common stock, par value $0.001 per share (the "Common Stock") and a private placement of warrants to purchase 1,317,060 shares of Common Stock. The shares of Common Stock and warrants were sold for a combined purchase price of $4.895 per unit for total net proceeds of $5.6 million. The warrants are exercisable beginning on the date of their issuance until November 29, 2024 at an initial exercise price equal to $5.00.

Also during the second quarter, Diffusion announced that based on favorable safety data in a 19-patient dose-escalation run-in study, the Data Safety Monitoring Board (DSMB) has recommended the continuation of the Company’s Phase 3 clinical trial with trans sodium crocetinate (TSC) in inoperable glioblastoma multiforme (GBM) patients. The DSMB has recommended that the highest dose administered, 1.5 mg/kg of TSC, be used during the adjuvant treatment period of the Phase 3 INTACT trial. The INTACT (INvestigating Tsc Against Cancerous Tumors) trial is comparing standard of care (SOC) radiation therapy and chemotherapy plus TSC against SOC alone. In Phase 2 testing, TSC demonstrated a nearly four-fold improvement in overall survival at two years for the subset of inoperable GBM patients compared with the control group of GBM patients. Diffusion is seeking a partner to continue development of TSC in GBM.

The Company completed preparations to commence enrollment in its on-ambulance Phase 2 clinical trial testing TSC for the treatment of acute stroke. Enrollment is expected to begin in the third quarter of 2019. With close cooperation of researchers at the University of California Los Angeles (UCLA) and the University of Virginia (UVA), the 160-patient trial, named PHAST-TSC (Pre-Hospital Administration of Stroke Therapy-TSC), will involve 23 hospitals across urban, suburban and rural areas in Los Angeles County and Central Virginia. Results from the trial may be available in just under two years.

The Company continued to enhance its intellectual property position during the quarter, with receipt from the European Patent Office of a Notice of Intention to Grant a patent related to the use of TSC in combination with the leading thrombolytic, tissue plasminogen activator (tPA), in the treatment of ischemic stroke. The patent claim covers administration of TSC within three or four hours of the onset of stroke symptoms in combination with tPA administered within nine to 12 hours of the onset of stroke symptoms. The European Patent Office has also granted two additional patents to Diffusion related to the uses of TSC and methods of synthesizing the compound.

"The imminent commencement of enrollment in our PHAST-TSC Phase 2 study comes after extensive preparation," said David Kalergis, chairman and chief executive officer of Diffusion. "It represents an exciting possibility to safely mitigate some of the devastating effects of a stroke through immediate, in-ambulance treatment. The Notice of Intention to Grant a patent from the European Patent Office for the use of TSC in combination with tPA – the only currently available drug for the treatment of ischemic stroke – further supports the commercial prospects of TSC.

"We were also pleased to complete a registered direct equity financing in May, at the market price, raising net proceeds of $5.6 million. These funds will largely be used to advance our clinical programs," Mr. Kalergis added.

Second Quarter Financial Results

Research and development expenses were $1.5 million for the second quarter of 2019, compared with $1.4 million for the second quarter of 2018. The increase was mainly attributable to a $0.6 million increase related to the commencement of the Phase 2 stroke trial and a $0.1 million increase in salary and manufacturing, offset by a $0.6 million decrease in expenses related to the Company’s Phase 3 GBM trial.

General and administrative expenses were $1.1 million for the second quarter of 2019, compared with $1.7 million for the second quarter of 2018. The decline was due to lower salary and wages and stock-compensation expense.

Net cash used in operating activities during the first half of 2019 was $5.3 million, compared with $5.8 million used during the prior-year period.

Diffusion had cash and cash equivalents of $8.4 million as of June 30, 2019, compared with $8.0 million at December 31, 2018. During the quarter, the Company raised $5.6 million net proceeds from an offering of 1,317,060 shares of common stock and warrants to purchase up to 1,317,060 shares of common stocks.

On August 8, 2019 Cytovation AS ("Cytovation") and Specialized Medical Services-oncology BV ("SMS-oncology") reported that SMS-oncology has been selected as the CRO to conduct the phase I/II clinical trial with CyPep-1 in patients with advanced solid cancers (Press release, Cytovation, AUG 8, 2019, View Source [SID1234561561]).

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In recent months, Cytovation has progressed through preclinical and toxicology studies with its lead candidate CyPep-1, a first-in-class lytic agent. Through its unique pharmacological properties, CyPep-1 selectively targets and lyses tumor cell membranes based on their altered molecular composition. This mode of action kills cancer cells, releases tumor antigens, and potentially induces a tumor-specific immune response by in-situ immunization.

Cytovation is currently initiating a first-in-human trial with intratumoral injection of CyPep-1 and aims to reach first in patient (FPI) milestone by the end of 2019. An agreement is now concluded with the oncology dedicated CRO SMS-oncology in Schiphol, the Netherlands.

The study is designed as an open-label, dose escalation phase I/II trial to evaluate the safety, efficacy and pharmacokinetics of intratumoral CyPep-1 in patients with advanced solid cancers. The multicenter trial in Europe will enroll approximately 18 patients. SMS-oncology is developing the protocol and giving guidance regarding patient inclusion criteria and investigational sites for a best-fit and seamless transition to clinic. This will be followed by full conduct of the trial, expected to commence in Q4 2019.

Mr. Kjell-Inge, CEO of Cytovation: "We are excited CyPep-1 is now progressing to the next phase of development, which is an important step for our company. We are pleased with selecting SMS-oncology as our partner in this transition to clinic. From the initial discussions, they lived up to their reputation as experts in the field of early phase and immuno-oncology trials. Preparations of the trial are moving forward in a fast pace, and we feel confident our trial will be conducted in an optimal and valuable matter with our goals is mind."

Ms. Philine van den Tol, CEO of SMS-oncology: "We are delighted to support Cytovation and look forward to jointly make the CyPep-1 trial a great success. It is exactly these type of innovative projects SMS-oncology leverages great experience in, and beyond all, is passionate
about. The enthusiasm of Cytovation is catching and our team can’t wait to see results of this promising first-in-class lytic compound."

CyPep-1, in a cream formulation for topical application, is currently being evaluated in a phase I trial in patients with HPV-induced cutaneous tumors (warts).

On August 8, 2019 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology (I-O) company with a pipeline of immune checkpoint antibodies, adoptive cell therapies1, and cancer vaccines provided corporate updates and reported financial results for the second quarter of 2019 (Press release, Agenus, AUG 8, 2019, View Source [SID1234538379]).

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"In the second quarter our progress continued at a rapid pace," said Garo H. Armen, Ph.D., Chairman and CEO of Agenus. "This year we delivered 2 INDs, initiated the interim analysis in our CTLA-4 & PD-1 trials, triggered cash milestones in our Gilead collaboration, advanced our next generation CTLA-4 in the clinic, and brought on board our head of commercial operations. We look forward to discussing all of these in more detail during our call and at our global R&D days in the next few months."

Achievements
Delivered on partnership programs; triggering additional cash milestones
Triggered $15 million from Gilead as milestone payment for IND acceptance of AGEN1423 (now GS-1423) & AGEN2373
CTLA-4 and PD-1 trials advancing – interim analysis underway
Trials in 2L cervical cancer designed to support BLA via accelerated pathway
Interim analysis underway; data readouts expected 2H2019
PD-1 market expansion planned through project-based financing
Enrollment proceeding in next-gen CTLA-4 trial
Clinical trial underway; combinations and early data expected this year
Advanced new discoveries towards the clinic
AGEN2373 IND accepted by FDA
Off-the shelf phosphorylated neoantigen vaccine advanced to IND
QS-21 Updates
Sales of Shingrix, containing our QS-21 Stimulon, continue to increase; GSK projects 2019 sales will exceed $1.3Bn
AgenTus Cell Therapy Business:
IND for allogeneic cell therapy on track for 2H2019
IND for autologous NYESO-1 planned for 2H2019; proprietary combinations with Agenus check point antibodies planned in 1H2020
Partnership and private financing discussions are underway
Second Quarter 2019 Financial Results

We ended the second quarter of 2019 with a cash balance of $122 million as compared to $53 million at December 31, 2018.

For the six months ended June 30, 2019, we reported a net loss of $34 million or $0.24 per share compared to a net loss for the same period in 2018 of $79 million or $0.76 per share. During the first half of the year we recognized revenue of $96 million which includes revenue from our transaction with Gilead and non-cash royalties earned and recorded $20 million of non-cash interest expense due to our liability related to the sale of future royalties. Our operating expenses for the first half of 2019 increased by $29 million as a result of the advancement of our programs.

For the second quarter ended June 30, 2019, we reported net loss of $52 million or $0.38 per share compared to a net loss for same period in 2018 of $25 million, or $0.24 per share.

Both periods results include one time and non-cash items.

Conference Call, Webcast and Prepared Statement Information

Date: Thursday, August 8, 2019
Time: 8:30 a.m. ET
Domestic Dial-in Number: (844) 492-3727
International Dial-in Number: (412) 317-5118
Conference ID: Agenus

Live Webcast: accessible from the Company’s website at View Source or with this link View Source

A replay will be available on the Company’s website approximately two hours after the call and will remain available for 90 days.